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Introduction: Genetic polymorphisms who disturb the mineral homeostasis during tooth development and eruption are candidate to clarify the molecular mechanisms involved in changes in the tooth eruption chronology. In this study, we evaluate whether the FokI (rs2228570) and BglI (rs739837) polymorphisms in the Vitamin D receptor (VDR) gene are associated with changes in the chronology of eruption of permanent teeth. Material & method: This cross-sectional study randomly included 353 biologically unrelated children, both sexes, without systemic impairment or syndromes and history of trauma during the primary dentition. One operator perform the oral clinical examination. The tooth was considered erupted if there was a visible minimum of any tooth surface emerging from the mucosa. Genomic DNA was extracted from buccal epithelial cells from saliva samples. Genotyping was performed by Real-Time Polymerase Chain Reactions using TaqMan® technology. The average of the total number of erupted permanent teeth between the genotypes was compared by the Mann-Whitney test and multivariate Generalized Linear Models (GLM) (α = 5 %). ß values with Confidence Interval (CI) 95 % were calculated. Results: The heterozygous adenine-guanine genotype of the FokI significantly decreases the number of erupted permanent teeth (ß = -1.15; CI 95 % = -2.22 to -0.07; p = 0.036). In the stratified analysis for maxillary and mandibular teeth, this genotype was associated with a decrease in the number of erupted maxillary permanent teeth (ß = -0.65; CI 95 % = -1.22 to -0.09; p = 0.023). BglI was not associated with permanent teeth eruption. Conclusion: The FokI, but not BglI, in the VDR may delay the eruption of permanent teeth.
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The methylenetetrahydrofolate reductase (MTHFR) gene 677CâT polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677CâT polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07-0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results.
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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.
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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 CatiónRESUMEN
Exploring genetic resources through genomic analyses has emerged as a powerful strategy to develop common bean (Phaseolus vulgaris L.) cultivars that are both productive and well-adapted to various environments. This study aimed to identify genomic regions linked to morpho-agronomic traits in Mesoamerican and Andean common bean accessions and to elucidate the proteins potentially involved in these traits. We evaluated 109 common bean accessions over three agricultural years, focusing on traits including the grain yield (YDSD), 100-seed weight (SW), number of seeds per pod (SDPD), number of pods per plant (PDPL), first pod insertion height (FPIH), plant height (PLHT), days to flowering (DF), and days to maturity (DPM). Using multilocus methods such as mrMLM, FASTmrMLM, FASTmrEMMA, ISIS EM-BLASSO, and pLARmEB, we identified 36 significant SNPs across all chromosomes (Pv01 to Pv11). Validating these SNPs and candidate genes in segregating populations is crucial for developing more productive common bean cultivars through marker-assisted selection.
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OBJECTIVE: To describe independent factors related to the interaction of FTO rs9939609, TMEM18 rs6548238, leptin, and adiponectin in children/adolescents with asthma, under the influence of obesity. METHODS: The authors performed a cross-sectional study with 57 children/adolescents, ages 8-19 years, at a tertiary hospital, from 2017 to 2018. Participants were classified by nutritional status, performed spirometry with a bronchodilator test and completed an asthma questionnaire, higher scores indicated more asthma symptoms. Two asthma groups were formed: Group 1(G1)-normal-weight; Group 2(G2)-overweight/obese. Serum was collected for adipokines (n = 32) and genetic polymorphisms (n = 53) dosages. RESULTS: Age and body mass index (BMI) correlated directly in normal-weight (p = 0.009) and obese participants (p = 0.004). Girls reported more asthma complaints (p = 0.044). Participants with negative bronchodilator responses presented lower BMI (14.55-17.16) than responders (19.4-26.84) (p = 0.049). Leptin dosages are related directly to BMI (5,34-40 ng/ml in obese × 0,54-42 ng/ml in nonobese) (p = 0.003). Levels were high in girls (4.78-17.55 µg/ml) (p = 0.029) and low in nonobese boys (0.54-6.92 µg/ml) (p = 0.006). In obese, low leptin levels (< 10 ng/ml) were found in small airway dysfunction carriers (p = 0.025); elevated adiponectin (> 5 µg/ml) correlated with FEV1/FVC > 80 % (p = 0.035) and positive bronchodilator tests (8.84-13 µg/ml) (p = 0.039); and FTO A allele correlated with low adiponectin 0-8.84 µg/ml (p = 0.021) and low FEV1/FVC (46 %-88 %) (p = 0.023). CONCLUSION: BMI correlated directly with age and leptin levels. Obese participants presented high serum levels of leptin and FTO A allele correlated with low FEV1/FVC. Larger cohorts are necessary for better elucidation of the role of adipokines and polymorphisms in the pathophysiology of asthma and obesity.
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Excessive weight (overweight and obesity) is a common disorder involving genetic and environmental factors, associated with cardiovascular diseases, type-2 diabetes, and others. NOTCH1 is critical for the maintenance of stem cells and adult tissues, being reported as a key player in metabolism and adipogenesis in animals. Thus, we test the hypothesis that NOTCH1 Single Nucleotide Polymorphisms (SNPs) are associated with excessive weight. Participants from the census-based cohort SABE (Saúde, Bem Estar e Envelhecimento-Health, Well-Being, and Aging), carried out in the city of São Paulo-Brazil, were stratified into cases and controls according to BMI. We filter the SNPs located at the start and end positions of NOTCH1 and 50 Kb on both sides. We selected SNPs with minor allelic frequency (MAF) greater than or equal to 0.01 and Hardy-Weinberg equilibrium (p > 0.05) and r2 ≥ 0.8. We performed an association study with genotypes and haplotypes, as well as in silico functional analysis of the identified SNPs. We observed an association of the SNP rs9411207 with the risk of excessive weight, under log-additive model, and the genotype distribution showed an increased frequency of homozygous TT (OR 1.50, CI 1.20-1.88; p = 0.0002). The haplotype GAT constructed from this and other SNPs in high Linkage Disequilibrium was more frequent in excessive-weight individuals (p = 0.003). In silico analyses suggested that these SNPs are likely to affect the transcription of NOTCH1 and other genes involved in adipogenesis and metabolism. This is the first study reporting association between NOTCH1 SNPs and the risk of excessive weight. Considering the possibility of NOTCH1 modulation, additional population studies are important to replicate these data and confirm the usefulness of risk genotypes for management strategies of excessive weight.
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Obesidad , Sobrepeso , Polimorfismo de Nucleótido Simple , Receptor Notch1 , Receptor Notch1/genética , Humanos , Brasil/epidemiología , Masculino , Obesidad/genética , Femenino , Anciano , Sobrepeso/genética , Predisposición Genética a la Enfermedad , Persona de Mediana Edad , Haplotipos , Frecuencia de los Genes , Estudios de Casos y Controles , Genotipo , Índice de Masa CorporalRESUMEN
Objectives: Our study evaluated the association of the polymorphism rs724016 in the ZBTB38 gene, previously associated with height in other populations, with predictors of height, clinical outcomes, and laboratory parameters in sickle cell anemia (SCA). Methods: Cross-sectional study with individuals with SCA and aged between 3 and 20 years. Clinical, laboratory, molecular, and bone age (BA) data were evaluated. Levels of IGF-1 and IGFBP-3 were adjusted for BA, target height (TH) was calculated as the mean parental height standard deviation score (SDS), and predicted adult height (PAH) SDS was calculated using BA. Results: We evaluated 80 individuals with SCA. The homozygous genotype of the G allele of rs724016 was associated with a lower height SDS (p < 0.001) and, in a additive genetic model, was negatively associated with HbF levels (p = 0.016). Lower adjusted IGF-1 levels were associated with co-inheritance of alpha-thalassemia and with the absence of HU therapy. Elevated HbF levels were associated with a lower deficit in adjusted growth potential (TH minus PAH). Conclusion: Our analysis shows that SNP rs724016 in the ZBTB38 is associated with shorter height and lower HbF levels, an important modifier of SCA.
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BACKGROUND: Diabetes mellitus is a chronic and multifactorial condition, including environmental risk factors such as lifestyle habits and genetic conditions. OBJECTIVE: We aimed to evaluate the association of VDR gene polymorphism (rs2228570) FokI and vitamin D levels with diabetes in adults. METHODS: Cross-sectional population-based study in adults, conducted from October to December 2020 in two Brazilian cities. The outcome variable was diabetes, defined as glycated hemoglobin ≥ 6.5% or self-report medical diagnosis or use of oral hypoglycemic drugs. Vitamin D (25-hydroxyvitamin D) was measured by indirect electrochemiluminescence, and classified as deficiency when 25(OH)D < 20 ng/mL. All participants were genotyped for VDR FokI polymorphism by qPCR and classified as homozygous mutant (ff or GG), heterozygous (Ff or AG), or homozygous wild (FF or AA). A combined analysis between the FokI polymorphism and vitamin D levels with diabetes was also examined. A directed acyclic graph (DAG) was used to select minimal and sufficient adjustment for confounding variables by the backdoor criterion. RESULTS: The prevalence of DM was 9.4% and vitamin D deficiency (VDD) was 19.9%. The genotype distribution of FokI polymorphism was 9.9% FF, 44.8% Ff, and 45.3% ff. It was possible to verify a positive association between vitamin D deficiency and DM (OR = 2.19; 95% CI: 1.06-4.50). Individuals with the altered allele (ff) had a 1.78 higher prevalence of DM (OR: 1.78; 95% CI; 1.10-2.87). Combined analyses, individuals with vitamin D deficiency and one or two copies of the altered FokI allele had a higher prevalence of DM (Ff + ff: OR: 1.67; 95% CI; 1.07-2.61; ff: OR: 3.60; 95% CI; 1.40-9.25). CONCLUSION: Our data suggest that vitamin D deficiency and FokI polymorphism are associated with DM.
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To evaluate association of vitamin D with sleep quality in adults and the influence of VDR-gene polymorphism FokI (rs2228570;A > G). Cross-sectional population-based study in adults, conducted in Brazil. The outcome was sleep-quality, evaluated by the Pittsburgh Sleep Quality Index. Vitamin D was determined by indirect electrochemiluminescence and classified as deficiency (VDD), 25(OH)D < 20 ng/mL in a healthy population or 25(OH)D < 30 ng/mL for groups at risk for VDD. FokI polymorphism in the VDR-gene was genotyped by qPCR and classified as homozygous wild (FF or AA), heterozygous (Ff or AG), or homozygous mutant (ff or GG). Multivariate logistic analysis was used to estimate the association between vitamin D and FokI polymorphism with sleep-quality. In a total of 1674 individuals evaluated, 53.6% had poor-sleep-quality, 31.5% had VDD, and the genotype frequency of the FokI polymorphism was 9.9% FF, 44.6% Ff, and 45.5% ff. In multivariate analysis, individuals with VDD had 1.51 times the chance of poor-sleep-quality, and individuals with the ff genotype had 1.49 times the chance of poor-sleep-quality (OR:1.49;95%CI:1.05-2.12) when compared to individuals with the FF or Ff genotype. In the combined analysis, individuals with VDD and ff genotype had more chance of poor-sleep-quality than individuals with sufficient vitamin D and genotype Ff or FF (OR:2.19;95%CI:1.27-3.76). Our data suggest that VDD and VDR FokI gene polymorphism are associated with poor-sleep-quality, and combining the two factors increases the chance of poor-sleep-quality compared to separate groups.
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Calidad del Sueño , Vitamina D , Adulto , Humanos , Estudios Transversales , Receptores de Calcitriol/genética , Polimorfismo Genético , Vitaminas , Genotipo , Predisposición Genética a la EnfermedadRESUMEN
PURPOSE: To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and also to verify the association between SNPs and the severity of RD. METHODS: This systematic review was reported according to the PRISMA guideline. The proportion meta-analysis was performed to identify the prevalence of genetic markers by geographical region and radiation dermatitis severity. The meta-analysis was performed to verify the association between genetic markers and RD severity. The certainty of the evidence was assessed by GRADE. RESULTS: Thirteen studies were included. The most prevalent SNPs were XRCC3 (rs861639) (36%), TGFß1 (rs1800469) (35%), and RAD51 (rs1801321) (34%). There are prevalence studies in Europe and Asia, with a similar prevalence for all SNPs (29-40%). The prevalence was higher in patients who developed radiation dermatitis ≤2 for any subtype of genes (75-76%). No SNP showed a statistically significant association with very low certainty of evidence. CONCLUSION: The most prevalent SNPs may be predictors of acute RD. The analysis of SNP before starting radiation therapy may be a promising method to predict the risk of developing radiation dermatitis and allow radiosensitive patients to have a customized treatment. This current review provides new research directions.
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Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Radiodermatitis , Humanos , Marcadores Genéticos/genética , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/genética , Radiodermatitis/genética , Factores de RiesgoRESUMEN
Numerous studies have established associations between single nucleotide polymorphisms (SNPs) and various behavioral and neurodevelopmental conditions. This study explores the links between SNPs in candidate genes involved in central nervous system (CNS) physiology and their implications for the behavioral and emotional aspects in children and teenagers. A total of 590 participants, aged 7-15 years, from the Early Life Exposures In Mexico To Environmental Toxicants (ELEMENT) cohort study in Mexico City, underwent genotyping for at least one of 15 CNS gene-related SNPs at different timepoints. We employed multiple linear regression models to assess the potential impact of genetic variations on behavioral and cognitive traits, as measured by the Behavioral Assessment System for Children (BASC) and Conners parent rating scales. Significant associations were observed, including the rs1800497 TC genotype (ANKK1) with the Cognitive Problems/Inattention variable (p value = 0.003), the rs1800955 CT genotype (DDR4) with the Emotional Lability Global index variable (p value = 0.01), and the rs10492138 GA and rs7970177 TC genotypes (GRIN2B) with the Depression variable (p values 0.007 and 0.012, respectively). These finds suggest potential genetic profiles associated with "risk" and "protective" behaviors for these SNPs. Our results provide valuable insights into the role of genetic variations in neurobehavior and highlight the need for further research in the early identification and intervention in individuals at risk for these conditions.
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Worldwide, gastric cancer (GC) is estimated to be the fifth most common type of cancer type in both sexes, ranking sixth for new cases, with >640,850 cases per year, and fourth in terms of mortality rate. Cancer presents numerical and structural alterations in chromosomes, often through gains and losses of regions. In GC, there are multiple genetic alterations, in which those located in cytoband 8q24 have been frequently described; essential genes are present in this cytoband, regulating the homeostasis of crucial biological processes, such as the MYC gene, which induces expression of selective genes to promote cell growth and proliferation. Conversely, DNA sequence variations can also occur when a single nucleotide in the genome sequence is altered, and this is termed a single nucleotide polymorphism (SNP). These alterations, which can serve as a biological marker, are present in at least 1% of the population and assist in identifying genes associated with GC. In the present review, 12 genes present in cytoband 8q24 related to GC (NSMCE2, PCAT1, CASC19, CASC8, CCAT2, PRNCR1, POU5F1B, PSCA, JRK, MYC, PVT1 and PTK2) are discussed. The PSCA gene was cited more frequently than others; it has four known SNPs associated with GC (rs2978980, rs2294008, rs2976392 and rs9297976). Thus, these SNPs should be further studied in different populations to determine their risk value in patients with GC.
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Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.
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OBJECTIVE: Fibulin-5 is a connective tissue component and may play a role in pelvic organ prolapse (POP) pathogenesis. This study aimed to verify the association of the rs2018736 polymorphism of the fibulin-5 gene with POP in postmenopausal Brazilian women, and to determine the risk factors for POP. METHOD: This observational, cross-sectional, case-control study assessed postmenopausal women with advanced POP (stages III and IV) and control women (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences were analyzed by real-time reverse-transcriptase polymerase chain reaction. A logistic regression model was used with p < 0.05 for significance. RESULTS: A total of 565 participants were evaluated (325 POP and 240 control). The homozygous C allele of rs2018736 (CC) was protective against POP (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.91). Age (OR 1.09, 95% CI 1.05-1.13), number of pregnancies (OR 1.14, 95% CI 1.01-1.28), vaginal delivery (OR 5.32, 95% CI 2.58-11.01), forceps delivery (OR 3.34, 95% CI 1.72-6.47), weight of newborn (OR 1.0007, 95% CI 1.0002-1.0011), family history of POP (OR 2.35, 95% CI 1.24-4.44), hypertension (OR 1.74, 95% CI 1.01-3.00) and diabetes (OR 2.19, 95% CI 1.07-4.48)] were independent predictors for POP; cesarean (OR 0.02, 95% CI 0.005-0.09) was protective. CONCLUSION: The rs2018736-CC genotype of the fibulin-5 gene has a protective role against POP.
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Proteínas de la Matriz Extracelular , Prolapso de Órgano Pélvico , Polimorfismo de Nucleótido Simple , Posmenopausia , Humanos , Femenino , Estudios de Casos y Controles , Prolapso de Órgano Pélvico/genética , Persona de Mediana Edad , Proteínas de la Matriz Extracelular/genética , Estudios Transversales , Posmenopausia/genética , Brasil , Factores de Riesgo , Anciano , Predisposición Genética a la Enfermedad , GenotipoRESUMEN
OBJECTIVE: Glucagon-like peptide-1 receptor belongs to the B family of G protein-coupled receptors, serving as a binding protein in membranes and is widely expressed in human tissues. Upon stimulation by its agonist, the glucagon-like peptide-1, the receptor plays a role in glucose metabolism, enhancing insulin secretion, and regulating appetite in the hypothalamus. Mutations in the glucagon-like peptide-1 receptor gene can lead to physiological changes that may explain phenotypic variations in individuals with obesity and diabetes. Therefore, this study aimed to evaluate missense variants of the glucagon-like peptide-1 receptor gene. METHODS: Data mining was performed on the single nucleotide polymorphism database, retrieving a total of 16,399 variants. Among them, 356 were missense. These 356 variants were analyzed using the PolyPhen-2 and filtered based on allele frequency, resulting in 6 pathogenic variants. RESULTS: D344E, A239T, R310Q, R227H, R421P, and R176G were analyzed using four different prediction tools. The D344E and A239T resulted in larger amino acid residues compared to their wild-type counterparts. The D344E showed a slightly destabilized structure, while A239T affected the transmembrane helices. Conversely, the R310Q, R227H, R421P, and R176G resulted in smaller amino acid residues than the wild-type, leading to a loss of positive charge and increased hydrophobicity. Particularly, the R421P, due to the presence of proline, significantly destabilized the α-helix structure and caused severe damage to the receptor. CONCLUSION: Elucidating the glucagon-like peptide-1 receptor variants and their potentially detrimental effects on receptor functionality can contribute to an understanding of metabolic diseases and the response to available pharmacological treatments.
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Diabetes Mellitus , Incretinas , Humanos , Aminoácidos , Glucagón , Receptor del Péptido 1 Similar al Glucagón/genética , Incretinas/metabolismo , Obesidad/genética , FenotipoRESUMEN
Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.
Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.
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Humanos , Farmacogenética , Trasplante de Hígado , Polimorfismo de Nucleótido Simple , Trasplante de Órganos , Tacrolimus , Rechazo de InjertoRESUMEN
This systematic review and meta-analysis aimed to verify the association between single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and the severity or mortality of coronavirus disease 19 (COVID-19). We systematically searched PubMed, BVS/Bireme, Scopus, Embase, and Web of Science for relevant studies published until November 24, 2023. Twelve studies were included. Thirty-one SNPs related to four genes were studied (VDR, 13 SNPs; GC, 6 SNPs; DHCR7/NADSYN1, 6 SNPs; CYP2R1, 6 SNPs). Eight SNPs were examined in two or more studies (VDR rs731236, rs2228570, rs1544410, rs7975232, rs739837, rs757343, rs11568820, and rs4516035). Meta-analysis showed a significant association between the VDR rs1544410 Bb + bb genotype and b allele and an increased odds of developing severe/critical COVID-19 (Bb + bb vs. BB = 2 studies, OR = 1.73, 95% confidence interval (CI): 1.16-2.57, P = 0.007, I2 = 0%; b allele vs. B allele = 2 studies, OR = 1.31, 95% CI: 1.03-1.67; P = 0.03; I2 = 0%). Regarding the mortality rate, VDR rs731236 TT-genotype, TT + Tt genotype, and T allele; VDR rs1544410 bb-genotype, Bb + bb genotype, and b allele; VDR rs7975232 AA-genotype, AA + Aa genotype, and A allele; and VDR rs2228570 ff-genotype, Ff + ff genotype, and f allele were associated with increased odds of death due to COVID-19. In conclusion, the present study suggests that SNPs rs1544410 may serve as a predictive biomarker for COVID-19 severity and rs731236, rs1544410, rs7975232, and rs2228570 as predictive biomarkers for COVID-19 mortality. More well-designed studies involving a larger number of COVID-19 patients are required to validate and replicate these findings.
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COVID-19 , Polimorfismo de Nucleótido Simple , Humanos , Predisposición Genética a la Enfermedad , Receptores de Calcitriol/genética , COVID-19/genética , Genotipo , Vitamina D/genéticaRESUMEN
Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16INK4a+ (p = 0.59) and high-risk HPV+ (p = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16INK4a+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR (p = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.
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Carcinoma de Células Escamosas , Infecciones por Papillomavirus , ARN Largo no Codificante , Masculino , Humanos , Metilación de ADN , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Carcinoma de Células Escamosas/genética , Carcinogénesis , ARN Largo no Codificante/genéticaRESUMEN
Abstract This study aims to identify single nucleotide polymorphisms (SNPs) within KRTAP genes in alpacas (Vicugna pacos), which play a fundamental role in defining their physico-mechanical properties and potentially the quality of alpaca fiber, the primary product of their breeding. Thirty-four KRTAP genes, as annotated in the reference genome VicPac3.1, were investigated. Utilizing the reference genome, along with nine additional genomes and reads from 300 reduced representation DNA libraries of alpacas, SNPs were identified. Minor allele frequency (MAF) and genotyping rates were computed using PLINK software, while Illumina Scores were determined for each SNP using Illumina Design Studio software. Markers meeting the criteria of MAF ≥ 0.05, genotyping rate > 45%, and Illumina Score ≥ 0.6 per SNP were selected. A total of 67 SNPs were identified within intronic, exonic, and untranslated regions of KRTAP genes. Among these, 35 SNPs were incorporated into the 76K Alpaca SNP microarray, with 32 SNPs subsequently validated in a population of 936 alpacas. In conclusion, our findings delineate SNPs within KRTAPs that hold potential utility in genome-wide association studies, thereby facilitating the integration of modern breeding technologies into alpaca breeding programs.
Resumen Este estudio tiene como objetivo identificar polimorfismos de nucleótido simple (PNSs) dentro de los genes KRTAP en alpacas (Vicugna pacos), que juegan un papel fundamental en la definición de sus propiedades físico-mecánicas y la calidad de la fibra de alpaca, producto principal de su crianza. Se investigaron treinta y cuatro genes KRTAP, tal como están anotados en el genoma de referencia VicPac3.1. Utilizando el genoma de referencia, junto con nueve genomas adicionales y lecturas de 300 bibliotecas de representación reducida de ADN de alpacas, se identificaron los PNSs. La frecuencia de los alelos menores (MAF) y las tasas de genotipificación se calcularon utilizando el software PLINK, mientras que los Illumina Score se determinaron para cada PNS utilizando el software Illumina Design Studio. Se seleccionaron marcadores que cumplían con los criterios de MAF ≥ 0.05, tasa de genotipado > 45% e Illumina Score ≥ 0.6 por PNS. Se identificaron un total de 67 PNSs dentro de regiones intrónicas, exónicas y/o no traducidas de genes KRTAP. Entre estos, se incorporaron 35 PNSs al microarray 76K Alpaca SNP, y posteriormente se validaron 32 PNSs en una población de 936 alpacas. En conclusión, nuestros hallazgos identificaron los PNSs dentro de los KRTAP que tienen una utilidad potencial en estudios de asociación de todo el genoma, facilitando así la integración de tecnologías de reproducción modernas en los programas de reproducción de alpacas.