RESUMEN

The Coastal Creole pigs in Argentina are predominantly found in the wild and can trace their lineage directly back to the Iberian breeds introduced by Spanish colonizers. They currently stand as the sole Creole breed in the country recognized by the FAO. However, there exists a dearth of studies assessing their genetic potential within the swine industry. Therefore, this study aimed to genetically characterize the meat quality of Coastal Creole pigs based on seven single nucleotide polymorphisms (SNPs) within the Ryr1, PRKAG3, MC4R, H-FABP, and CAST genes. A total of N = 158 samples were collected from specimens distributed along the coastal region. Our findings revealed all loci to exhibit polymorphism, underscoring the population's remarkable genetic diversity. Furthermore, a higher frequency of alleles favorable for the PRKAG3191I>V/200R>Q, MC4R1426A>G, CAST76872G>A, and Ryr11843C>T genes was observed, while alleles unfavorable predominated for H-FABP1811G>C and CAST638Ser>Arg. The results obtained in this research are highly encouraging, reflecting the genetic potential of these pigs to be utilized in swine production programs.

Asunto(s)

Polimorfismo de Nucleótido Simple , Sus scrofa , Animales , Argentina , Sus scrofa/genética , Carne/análisis , Canal Liberador de Calcio Receptor de Rianodina/genética

RESUMEN

Cassava (Manihot esculenta Crantz) is a vital carbohydrate source for over 800 million people globally, yet its production in East Africa is severely affected by cassava brown streak disease (CBSD). Genebanks, through ex-situ conservation, play a pivotal role in preserving crop diversity, providing crucial resources for breeding resilient and disease-resistant crops. This study genotyped 234 South American cassava accessions conserved at the CIAT genebank, previously phenotyped for CBSD resistance by an independent group, to perform a genome-wide association analysis (GWAS) to identify genetic variants associated with CBSD resistance. Our GWAS identified 35 single nucleotide polymorphism (SNP) markers distributed across various chromosomes, associated with disease severity or the presence/absence of viral infection. Markers were annotated within or near genes previously identified with functions related to pathogen recognition and immune response activation. Using the SNP candidates, we screened the world's largest cassava collection for accessions with a higher frequency of favorable genotypes, proposing 35 accessions with potential resistance to CBSD. Our results provide insights into the genetics of CBSD resistance and highlight the importance of genetic resources to equip breeders with the raw materials needed to develop new crop varieties resistant to pests and diseases.

Asunto(s)

Resistencia a la Enfermedad , Estudio de Asociación del Genoma Completo , Manihot , Enfermedades de las Plantas , Polimorfismo de Nucleótido Simple , Manihot/genética , Manihot/virología , Manihot/parasitología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/virología , América del Sur , Genotipo , Genoma de Planta , Potyviridae

RESUMEN

BACKGROUND/OBJECTIVES: Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables. METHODS: The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model. RESULTS: No significant associations were found between the SNPs ABCA1, ADIPOQ, FTO, and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ2 = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08-2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant (p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = -26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL). CONCLUSIONS: A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease.

Asunto(s)

LDL-Colesterol , Obesidad , Polimorfismo de Nucleótido Simple , Relación Cintura-Cadera , Humanos , Femenino , Masculino , México , Adulto , Obesidad/genética , Obesidad/sangre , Persona de Mediana Edad , LDL-Colesterol/sangre , Predisposición Genética a la Enfermedad , Adiponectina/sangre , Adiponectina/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Receptores de Leptina/genética , Factores de Riesgo , Antropometría , Genotipo , Transportador 1 de Casete de Unión a ATP

RESUMEN

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (<10 years or ≥10 years). Genotypes were determined by real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17-6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM.

Asunto(s)

Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Proteína Adaptadora GRB2 , Polimorfismo de Nucleótido Simple , Humanos , Retinopatía Diabética/genética , Proteína Adaptadora GRB2/genética , Masculino , Persona de Mediana Edad , Femenino , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Estudios de Casos y Controles , Anciano , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Brasil

RESUMEN

The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.

Asunto(s)

Predisposición Genética a la Enfermedad , Neuroblastoma , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/sangre , Neuroblastoma/genética , Neuroblastoma/sangre , Neuroblastoma/mortalidad , Neuroblastoma/patología , Masculino , Femenino , México , Preescolar , Lactante , Niño , Pronóstico , Genotipo , Estudios de Cohortes , Estudios de Casos y Controles

RESUMEN

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and B-cell ALL (B-ALL) is the most common subtype. The understanding of ALL has advanced significantly in recent years due to genomic sequencing, which has made it possible to identify genetic variants and detect the association between "single nucleotide polymorphisms" (SNP) and certain diseases. METHODS: We evaluated 126 patients diagnosed with B-ALL in hospitals in Rio de Janeiro. We described the frequency of polymorphisms in the IKZF1, CDKN2A/2B genes, the contribution of these genetic variants in pediatric ALL, and compared them with the general population of Rio de Janeiro. RESULTS: We demonstrated that the SNPs rs3731217, rs4132601, and rs11978267 were more frequent in patients with B-ALL. CONCLUSIONS: These findings contribute to a more complete understanding of B-ALL. They can guide future studies, bringing new perspectives on personalized therapies with reduced side effects and optimization efficacy of B-ALL treatment in children.

Asunto(s)

Inhibidor p15 de las Quinasas Dependientes de la Ciclina , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Factor de Transcripción Ikaros , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Factor de Transcripción Ikaros/genética , Masculino , Niño , Femenino , Brasil/epidemiología , Preescolar , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Adolescente , Lactante , Prevalencia , Predisposición Genética a la Enfermedad , Frecuencia de los Genes

RESUMEN

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Asunto(s)

Neoplasias de la Mama , Glucuronosiltransferasa , Estrés Oxidativo , Plaguicidas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Estrés Oxidativo/efectos de los fármacos , Plaguicidas/toxicidad , Persona de Mediana Edad , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Adulto , Pronóstico , Exposición Profesional/efectos adversos , Anciano , Alelos , Peroxidación de Lípido/efectos de los fármacos , Polimorfismo de Nucleótido Simple

RESUMEN

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research's importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process.

Asunto(s)

Predisposición Genética a la Enfermedad , Virus de la Hepatitis B , Hepatitis B , Interleucinas , Polimorfismo de Nucleótido Simple , Humanos , Brasil/epidemiología , Masculino , Interleucinas/genética , Femenino , Adulto , Virus de la Hepatitis B/genética , Hepatitis B/genética , Hepatitis B/virología , Persona de Mediana Edad , Alelos , Frecuencia de los Genes , Genotipo , Interferón lambda

RESUMEN

Colombian Creole pigs have adapted to tropical conditions for over 500 years. They have been modified by natural and artificial selection in different regions. At present, the diversity and current introgression status are unknown. The objective was to estimate the genomic diversity, linkage disequilibrium, population structure, and admixture of four Colombian pig breeds and their relationship with other breeds worldwide. Three Colombian pig breeds (SPE-San Pedreño, 11 samples; ZUN-Zungo, 11 samples; CM-Casco de Mula, ten samples) from the conservation nucleus and one biotype not recognized as a breed (CCH-Criollo Chocoano, seven samples) were genotyped using the Illumina GGP-Porcine80K chip. Open-access data from seven international breeds were also included. Colombian Creole pigs showed moderate genetic differentiation (FST 0.14) globally, but several groups of animals separated, suggesting local clustering due to geographical isolation or different founding effects. Colombian Creole pigs showed breed imprinting and specific grouping in all analyses except for CCH, which, like the Ecuadorian Creole, was a cluster of admixtures. The Colombian Creole pigs revealed a significant relationship with the Iberian pig and some other breeds to varying degrees. However, good maintenance of the conservation nucleus was evidenced. Potential adaptive genes, mainly related to immunological functions, were found, according to FST and pcadapt analyses. This study provides a foundation and scientific data for policy decisions on zoogenetic resources.

Asunto(s)

Variación Genética , Desequilibrio de Ligamiento , Sus scrofa , Animales , Colombia , Sus scrofa/genética , Genotipo , Cruzamiento , Polimorfismo de Nucleótido Simple , Genoma

RESUMEN

BACKGROUND: Nelore cattle play a key role in tropical production systems due to their resilience to harsh conditions, such as heat stress and seasonally poor nutrition. Monitoring their genetic diversity is essential to manage the negative impacts of inbreeding. Traditionally, inbreeding and inbreeding depression are assessed by pedigree-based coefficients (F), but recently, genetic markers have been preferred for their precision in capturing the inbreeding level and identifying animals at risk of reduced productive and reproductive performance. Hence, we compared the inbreeding and inbreeding depression for productive and reproductive performance traits in Nelore cattle using different inbreeding coefficient estimation methods from pedigree information (FPed), the genomic relationship matrix (FGRM), runs of homozygosity (FROH) of different lengths (> 1 Mb (genome), between 1 and 2 Mb - FROH 1-2; 2-4 Mb FROH 2-4 or > 8 Mb FROH >8) and excess homozygosity (FSNP). RESULTS: The correlation between FPed and FROH was lower when the latter was based on shorter segments (r = 0.15 with FROH 1-2, r = 0.20 with FROH 2-4 and r = 0.28 with FROH 4-8). Meanwhile, the FPed had a moderate correlation with FSNP (r = 0.47) and high correlation with FROH >8 (r = 0.58) and FROH-genome (r = 0.60). The FROH-genome was highly correlated with inbreeding based on FROH>8 (r = 0.93) and FSNP (r = 0.88). The FGRM exhibited a high correlation with FROH-genome (r = 0.55) and FROH >8 (r = 0.51) and a lower correlation with other inbreeding estimators varying from 0.30 for FROH 2-4 to 0.37 for FROH 1-2. Increased levels of inbreeding had a negative impact on the productive and reproductive performance of Nelore cattle. The unfavorable inbreeding effect on productive and reproductive traits ranged from 0.12 to 0.51 for FPed, 0.19-0.59 for FGRM, 0.21-0.58 for FROH-genome, and 0.19-0.54 for FSNP per 1% of inbreeding scaled on the percentage of the mean. When scaling the linear regression coefficients on the standard deviation, the unfavorable inbreeding effect varied from 0.43 to 1.56% for FPed, 0.49-1.97% for FGRM, 0.34-2.2% for FROH-genome, and 0.50-1.62% for FSNP per 1% of inbreeding. The impact of the homozygous segments on reproductive and performance traits varied based on the chromosomes. This shows that specific homozygous chromosome segments can be signs of positive selection due to their beneficial effects on the traits. CONCLUSIONS: The low correlation observed between FPed and genomic-based inbreeding estimates suggests that the presence of animals with one unknown parent (sire or dam) in the pedigree does not account for ancient inbreeding. The ROH hotspots surround genes related to reproduction, growth, meat quality, and adaptation to environmental stress. Inbreeding depression has adverse effects on productive and reproductive traits in Nelore cattle, particularly on age at puberty in young bulls and heifer calving at 30 months, as well as on scrotal circumference and body weight when scaled on the standard deviation of the trait.

Asunto(s)

Genómica , Depresión Endogámica , Endogamia , Linaje , Animales , Bovinos/genética , Genómica/métodos , Homocigoto , Femenino , Masculino , Polimorfismo de Nucleótido Simple

RESUMEN

Despite significant advances in the management of coronary artery disease (CAD) and reductions in annual mortality rates in recent decades, this disease remains the leading cause of death worldwide. Consequently, there is an ongoing need for efforts to address this situation. Current clinical algorithms to identify at-risk patients are particularly inaccurate in moderate-risk individuals. For this reason, the need for ancillary tests has been suggested, including predictive genetic screening. As genetic studies rapidly expand and genomic data becomes more accessible, numerous genetic risk scores have been proposed to identify and evaluate an individual's susceptibility to developing diseases, including CAD. The field of genetics has indeed made substantial contributions to risk prediction, particularly in cases where children have parents with premature CAD, resulting in an increased risk of up to 75%. The polygenic risk scores (PRSs) have emerged as a potentially valuable tool for understanding and stratifying an individual's genetic risk. The PRS is calculated as a weighted sum of single-nucleotide variants present throughout the human genome, identifiable through genome-wide association studies, and associated with various cardiometabolic diseases. The use of PRSs holds promise, as it enables the development of personalized strategies for preventing or diagnosing specific pathologies early. Furthermore, it can complement existing clinical scores, increasing the accuracy of individual risk prediction. Consequently, the application of PRSs has the potential to impact the costs and adverse outcomes associated with CAD positively. This narrative review provides an overview of the role of PRSs in the context of CAD.

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Apesar dos avanços significativos no tratamento da doença arterial coronariana (DAC) e das reduções nas taxas de mortalidade anuais nas últimas décadas, a DAC continua sendo a principal causa de morte no mundo. Consequentemente, há uma necessidade contínua de esforços para abordar essa situação. Os algoritmos clínicos atuais para identificar pacientes em risco são particularmente imprecisos para indivíduos de risco moderado. Por esse motivo, foi sugerido que são necessários testes auxiliares, incluindo triagem genética preditiva. À medida que os estudos genéticos se expandem rapidamente e os dados genômicos se tornam mais acessíveis, diversos escores de risco genético têm sido propostos para identificar e avaliar a suscetibilidade de um indivíduo ao desenvolvimento de doenças, incluindo a DAC. De fato, o campo da genética tem contribuído substancialmente para a previsão de risco, particularmente nos casos em que as crianças têm genitores com DAC prematura, resultando em um risco aumentado de até 75%. Os escores de risco poligênico (PRSs, do inglês polygenic risk scores) surgiram como uma ferramenta potencialmente valiosa para compreender e estratificar o risco genético de um indivíduo. O PRS é calculado como uma soma ponderada de variantes de nucleotídeo único presentes em todo o genoma humano, identificáveis por meio de estudos de associação genômica ampla, e associadas a várias doenças cardiometabólicas. O uso dos PRSs é promissor, pois permite o desenvolvimento de estratégias personalizadas para prevenir ou diagnosticar patologias específicas de forma precoce. Ademais, seu uso é capaz de complementar os escores clínicos existentes, aumentando a precisão da previsão de risco individual. Consequentemente, a aplicação dos PRSs tem o potencial de impactar positivamente os custos e os desfechos adversos associados à DAC. A presente revisão narrativa oferece uma visão ampla do papel dos PRSs no contexto da DAC.

Asunto(s)

Enfermedad de la Arteria Coronaria , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Humanos , Enfermedad de la Arteria Coronaria/genética , Medición de Riesgo/métodos , Predisposición Genética a la Enfermedad/genética , Herencia Multifactorial/genética , Factores de Riesgo , Pruebas Genéticas/métodos , Polimorfismo de Nucleótido Simple/genética , Puntuación de Riesgo Genético

RESUMEN

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory disease that affects the spine and can cause peripheral arthritis, enthesitis, and dactylitis, as well as extra-articular manifestations such as uveitis and inflammatory bowel disease. ß-Defensins are antimicrobial peptides involved in the activation and regulation of several immune cell types that may influence the inflammatory response in AS. The aim was to analyze the association and interaction of two functional variants of the DEFB1 gene in AS patients, and their role with inflammatory markers. METHODS AND RESULTS: The rs11362 and rs1800972 variants were genotyped using TaqMan probes in Mexican AS patients and controls. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were quantified. SPSS software was used for statistical analysis and multifactor dimensionality reduction (MDR) for interactions. The AA and GG genotypes were associated with AS risk in the age- and sex-adjusted model (OR = 6.89, P = 0.008 and OR = 3.43, P = 0.046, respectively); furthermore, the A-G haplotype showed a significant association with AS risk (OR = 2.94, P = 0.012). ESR and CRP were elevated in carriers of the AA genotype compared to the GA and GG genotypes of the rs11362 variant (20.89 ± 9.78 vs. 5.63 ± 4.61 and 4.10 ± 2.65 mm/h, P < 0.0001; and 10.92 ± 14.09 vs. 2.14 ± 2.02 and 2.15 ± 2.13 mg/L, P < 0.001, respectively). Using the MDR method, strong interactions of the rs11362 variant with sex were identified in the adjusted and unadjusted models. CONCLUSIONS: These results suggest that the DEFB1 gene may play a key role in AS pathogenesis.

Asunto(s)

Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante , beta-Defensinas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Alelos , beta-Defensinas/genética , Sedimentación Sanguínea , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Genotipo , Haplotipos/genética , México , Espondilitis Anquilosante/genética

RESUMEN

BACKGROUND: Recent studies have suggested an association between H. pylori and metabolic-disfunction associated fatty liver disease (MASLD). However, epidemiologic studies have yielded inconsistent results. We aim to evaluate the association of H. pylori and G-allele PNPLA3 in MASLD diagnosis, and markers of severity. METHODS: A multi-center cross-sectional study was conducted. A total 224 functional dyspepsia (FD) patients cohort who underwent gastroscopy was selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, LSM by VCTE, gastric biopsies, H. pylori status, and rs738409 PNPLA3 were evaluated. A second retrospective cohort of 86 patients with biopsy-proven MASLD who underwent gastroscopy with gastric biopsies was analyzed. RESULTS: In the FD cohort MASLD was observed in 52%, and H. pylori-positive in 51%. H. pylori infection was associated with MASLD prevalence, but in multivariate analyses adjusted for G-allele PNPLA3, it became not significant. Then in MASLD-only dyspeptic cohort, H. pylori infection was significantly linked to elevated serum AST levels and increased liver stiffness measurements, suggesting a potential role in liver injury and fibrosis. Histopathological analysis in biopsy-proven MASLD patients further supported these findings, showing a significant association between H. pylori infection and increased NAS score, fibrosis stage, and prevalence of MASH. Notably, the combination of H. pylori infection and G-allele PNPLA3 appeared to exacerbate MASLD severity beyond individual effects. CONCLUSIONS: Our results suggest that H. pylori infection may play a role in the progression of liver injury and fibrosis in patients with MASLD, especially in those with specific genetic predispositions.

Asunto(s)

Infecciones por Helicobacter , Helicobacter pylori , Lipasa , Proteínas de la Membrana , Humanos , Masculino , Femenino , Lipasa/genética , Proteínas de la Membrana/genética , Persona de Mediana Edad , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Adulto , Estudios Transversales , Estudios Retrospectivos , Hígado Graso/genética , Hígado Graso/complicaciones , Alelos , Polimorfismo de Nucleótido Simple , Dispepsia/microbiología , Dispepsia/genética , Dispepsia/complicaciones , Hígado/patología , Hígado/metabolismo , Aciltransferasas , Fosfolipasas A2 Calcio-Independiente

RESUMEN

BACKGROUND: African mahogany species (Khaya sp.) have been introduced to Brazil gaining increasing economic interest over the last years, as they produce high quality wood for industrial applications. To this date, however, the knowledge available on the genetic basis of African mahogany plantations in Brazil is limited, which has driven this study to examine the extent of genetic diversity and structure of three cultivated species (Khaya grandifoliola, Khaya senegalensis and Khaya ivorensis) and their prospects for forest breeding. RESULTS: In total, 115 individuals were genotyped (48 of K. grandifoliola, 34 of K. senegalensis and 33 of K. ivorensis) for 3,330 filtered neutral loci obtained from genotyping-by-sequencing for the three species. The number of SNPs varied from 2,951 in K. ivorensis to 4,754 in K. senegalensis. Multiloci clustering, principal component analysis, Bayesian structure and network analyses showed a clear genetic separation among the three species. Structure analysis also showed internal structure within each species, highlighting genetic subgroups that could be sampled for selecting distinct genotypes for further breeding, although the genetic distances are moderate to low. CONCLUSION: In our study, SNP markers efficiently assessed the genomic diversity of African mahogany forest plantations in Brazil. Our genetic data clearly separated the three Khaya species. Moreover, pairwise estimates of genetic distances among individuals within each species showed considerable genetic divergence among individuals. By genotyping 115 pre-selected individuals with desirable growth traits, allowed us not only to recommend superior genotypes but also to identify genetically distinct individuals for use in breeding crosses.

Asunto(s)

Bosques , Variación Genética , Brasil , Meliaceae/genética , Polimorfismo de Nucleótido Simple , Fitomejoramiento , Genotipo , Genoma de Planta

RESUMEN

Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by decreased insulin secretion and the development of insulin resistance. Previous genome-wide association studies demonstrated that single-nucleotide polymorphisms (SNPs) present in genes coding for ion channels involved in insulin secretion increase the risk of developing this disease. We determined the association of 16 SNPs found in CACNA1D, KCNQ1, KCNJ11, and CACNA1E genes and the increased probability of developing T2DM. In this work, we performed a case-control study in 301 Mexican adults, including 201 cases with diabetes and 100 controls without diabetes. Our findings indicate a moderate association between T2DM and the C allele, and the C/C genotype of rs312480 within CACNA1D. The CAG haplotype surprisingly showed a protective effect, whereas the CAC and CGG haplotypes have a strong association with T2DM. The C allele and C/C genotype of rs5219 were significantly associated with diabetes. Also, an association was observed between diabetes and the A allele and the A/A genotype of rs3753737 and rs175338 in CACNA1E. The TGG and CGA haplotypes were also found to be significantly associated. The findings of this study indicate that the SNPs examined could serve as a potential diagnostic tool and contribute to the susceptibility of the Mexican population to this disease.

Asunto(s)

Canales de Calcio Tipo L , Diabetes Mellitus Tipo 2 , Predisposición Genética a la Enfermedad , Canal de Potasio KCNQ1 , Polimorfismo de Nucleótido Simple , Canales de Potasio de Rectificación Interna , Humanos , Diabetes Mellitus Tipo 2/genética , Canales de Calcio Tipo L/genética , Canal de Potasio KCNQ1/genética , Femenino , Masculino , Canales de Potasio de Rectificación Interna/genética , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Haplotipos , Canales de Calcio Tipo R/genética , Alelos , México , Anciano , Estudios de Asociación Genética , Genotipo , Frecuencia de los Genes , Proteínas de Transporte de Catión

RESUMEN

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084-rs11692782-rs4784165, as well as a redundancy in rs7371084-rs11692782-rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.

Asunto(s)

Epistasis Genética , Predisposición Genética a la Enfermedad , Síndrome del Ovario Poliquístico , Polimorfismo de Nucleótido Simple , Humanos , Síndrome del Ovario Poliquístico/genética , Femenino , Adulto , Colombia/epidemiología , Estudio de Asociación del Genoma Completo , Estudios de Casos y Controles , Genotipo , Adulto Joven

RESUMEN

BACKGROUND: Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) plays a critical role in the ecology and economy of Western North America. This conifer species comprises two distinct varieties: the coastal variety (var. menziesii) along the Pacific coast, and the interior variety (var. glauca) spanning the Rocky Mountains into Mexico, with instances of inter-varietal hybridization in Washington and British Columbia. Recent investigations have focused on assessing environmental pressures shaping Douglas-fir's genomic variation for a better understanding of its evolutionary and adaptive responses. Here, we characterize range-wide population structure, estimate inter-varietal hybridization levels, identify candidate loci for climate adaptation, and forecast shifts in species and variety distribution under future climates. RESULTS: Using a custom SNP-array, we genotyped 540 trees revealing four distinct clusters with asymmetric admixture patterns in the hybridization zone. Higher genetic diversity observed in coastal and hybrid populations contrasts with lower diversity in inland populations of the southern Rockies and Mexico, exhibiting a significant isolation by distance pattern, with less marked but still significant isolation by environment. For both varieties, we identified candidate loci associated with local adaptation, with hundreds of genes linked to processes such as stimulus response, reactions to chemical compounds, and metabolic functions. Ecological niche modeling revealed contrasting potential distribution shifts among the varieties in the coming decades, with interior populations projected to lose habitat and become more vulnerable, while coastal populations are expected to gain suitable areas. CONCLUSIONS: Overall, our findings provide crucial insights into the population structure and adaptive potential of Douglas-fir, with the coastal variety being the most likely to preserve its evolutionary path throughout the present century, which carry implications for the conservation and management of this species across their range.

Asunto(s)

Pseudotsuga , Pseudotsuga/genética , Adaptación Fisiológica/genética , Variación Genética/genética , Hibridación Genética , Selección Genética , México , Polimorfismo de Nucleótido Simple , Colombia Británica

RESUMEN

OBJECTIVE: Ghrelin is an adipokine the placenta generates to control the maternal metabolic adaptation to pregnancy. It causes different pregnancy complications like preeclampsia (PE). Therefore, the aim of this study was to assess the association between ghrelin mRNA expression and rs26311 and rs27647 polymorphisms and PE development. METHODS: In total, 156 PE women (including 97 patients with mild PE and 59 patients with severe PE) and 152 healthy controls were recruited in this case-control study during 2019-2020. All participants with other diseases have been excluded from both groups. The ghrelin expression was analyzed with real-time PCR, and ghrelin variants were examined using the RFLP-PCR method. RESULTS: The maternal and placental ghrelin rs27647 and rs26311 variants were unrelated to PE susceptibility. Haplotype analyses showed no significant difference between the four haplotypes and PE. No relationship was revealed between rs27647 polymorphism and severe PE. However, the results indicated a relationship between rs27647 and severe PE compared to mild PE and controls. Therefore, the rs27647 variant was associated with severe PE compared to mild PE in codominant, recessive, and log-additive models and controls in codominant, dominant, recessive, and log-additive models. The placental ghrelin mRNA expression declined in PE women compared to controls (0.67-fold), but the difference was insignificant (p=0.263). No significant difference was found between various genotypes of rs27647 and rs26311 polymorphisms concerning ghrelin mRNA expression. CONCLUSION: The maternal and placental ghrelin polymorphisms, rs27647 and rs26311, showed no effect on PE. However, the rs27647 variant was associated with severe PE.

Asunto(s)

Predisposición Genética a la Enfermedad , Ghrelina , Polimorfismo de Nucleótido Simple , Preeclampsia , ARN Mensajero , Índice de Severidad de la Enfermedad , Humanos , Femenino , Preeclampsia/genética , Ghrelina/genética , Embarazo , Estudios de Casos y Controles , Adulto , Predisposición Genética a la Enfermedad/genética , ARN Mensajero/genética , Haplotipos , Genotipo , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven

RESUMEN

Understanding the combined effects of environmental heterogeneity and evolutionary processes on marine populations is a primary goal of seascape genomic approaches. Here, we utilized genomic approaches to identify local adaptation signatures in Littoraria flava, a widely distributed marine gastropod in the tropical West Atlantic population. We also performed molecular evolution analyses to investigate potential selective signals across the genome. After obtaining 6,298 and 16,137 single nucleotide polymorphisms derived from genotyping-by-sequencing and RNA sequencing, respectively, 69 from genotyping-by-sequencing (85 specimens) and four from RNA sequencing (40 specimens) candidate single nucleotide polymorphisms were selected and further evaluated. The correlation analyses support different evolutionary pressures over transcribed and non-transcribed regions. Thus, single nucleotide polymorphisms within transcribed regions could account for the genotypic and possibly phenotypic divergences in periwinkles. Our molecular evolution tests based on synonymous and non-synonymous ratio (kN/kS) showed that genotype divergences containing putative adaptive single nucleotide polymorphisms arose mainly from synonymous and/or UTR substitutions rather than polymorphic proteins. The distribution of genotypes across different localities seems to be influenced by marine currents, pH, and temperature variations, suggesting that these factors may impact the species dispersion. The combination of RNA sequencing and genotyping-by-sequencing derived datasets provides a deeper understanding of the molecular mechanisms underlying selective forces responses on distinct genomic regions and could guide further investigations on seascape genomics for non-model species.

Asunto(s)

Adaptación Fisiológica , Evolución Molecular , Gastrópodos , Polimorfismo de Nucleótido Simple , Animales , Gastrópodos/genética , Adaptación Fisiológica/genética , Genómica , Genotipo , Genoma

RESUMEN

The seascape comprises multiple environmental variables that interact with species biology to determine patterns of spatial genetic variation. The environment imposes spatially variable selective forces together with homogenizing and diverging drivers that facilitate or restrict dispersal, which is a complex, time-dependent process. Understanding how the seascape influences spatial patterns of genetic variation remains elusive, particularly in coastal upwelling systems. Here, we combine genome-wide SNP data, Lagrangian larval dispersal simulated over a hydrodynamic model, and ocean environmental information to quantify the relative contribution of ocean circulation and environmental heterogeneity as drivers of the spatial genetic structure of two congeneric intertidal limpets, Scurria scurra and S. araucana, along the central coast of Chile. We find that a genetic break observed in both limpet species coincides with a break in connectivity shown by the Lagrangian dispersal, suggesting that mean ocean circulation is an important seascape feature, in particular for S. scurra. For S. araucana, environmental variation appears as a better predictor of genetic structure than ocean circulation. Overall, our study shows broad patterns of seascape forcing on genetic diversity and contributes to our understanding of the complex ecological and evolutionary interactions along coastal upwelling systems.

Asunto(s)

Ecosistema , Variación Genética , Animales , Oceanografía , Gastrópodos/genética , Gastrópodos/fisiología , Chile , Océanos y Mares , Polimorfismo de Nucleótido Simple