RESUMO
Spinocerebellar ataxia type 10 (SCA10) is characteri- zed by ataxia, psychiatric disorders convulsions, and locus at 22q13.311. It is caused by expansions between 800-4500 pentanucleotide ATTCT repeats in intron 9 of the ATXN10 gene1-2. The ATXN10 gene encodes ataxin-10 protein (known as E46L) involved in neuritogenesis 1. SCA10 has a founder origin in Mexican, Brazilian, Argentine populattons but is rare in others.
Assuntos
Ataxias Espinocerebelares , Ideação Suicida , Ataxina-10 , Expansão das Repetições de DNA , Feminino , Humanos , México , Ataxias Espinocerebelares/genéticaRESUMO
The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15-30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4-9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far.
Assuntos
Etnicidade/genética , Genoma Humano , Migração Humana/história , Indígenas Norte-Americanos/genética , Filogenia , Dinâmica Populacional/estatística & dados numéricos , Etnicidade/classificação , Variação Genética , Genômica/métodos , História Antiga , Humanos , Indígenas Norte-Americanos/classificação , México , FilogeografiaRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has become a serious global health problem and numerous studies are currently being conducted to improve understanding of the components of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, as well as to identify solutions that mitigate the effects of COVID-19 symptoms. The nutritional supplement Vita Deyun® is composed of silymarin, glutathione, vitamin C and selenium. Studies of its individual components have demonstrated their benefits as anti-inflammatory agents, antioxidants and enhancers of the immune response. Therefore, the present study aimed to evaluate the in vitro effects of Vita Deyun on the expression of angiotensin-converting enzyme 2 (ACE2) in diverse cell lines, as well as in the presence or absence of the SARS-CoV-2 open reading frame (ORF)3a protein. Through reverse transcription-quantitative PCR, the use of viral particles containing SARS-CoV-2 ORF3a and bioinformatics analysis via the National Center for Biotechnology Information databases, ACE2 was determined to be highly expressed in oral and skin epithelial cells, with a lower expression observed in lung cells. Notably, the expression of SARS-CoV-2 ORF3a increased the level of ACE2 expression and Vita Deyun treatment diminished this effect. In addition, Vita Deyun treatment markedly decreased interleukin-18 mRNA levels. The combination of phytonutrients in Vita Deyun may help to boost the immune system and could reduce the effects of COVID-19. Ongoing clinical studies are required to provide evidence of the efficacy of Vita Deyun.
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The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.
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Introduction: Polymorphisms in the CETP gene promoter have been associated with cardiovascular risk and lipid alterations; however, their role in the development of hypertension has not been extensively explored. We evaluated four polymorphisms of the CEPT gene -827C>T, -631C>A, -630C>A, and -629C>A in patients with essential hypertension (EH). Materials and Methods: A total of 160 hypertensive (HT) patients and 160 normotensive (NT) individuals were studied. Blood pressure was measured and blood samples were collected for biochemical anlayses and DNA extraction. Polymorphisms were identified using Sanger sequencing. Genotype, genotype combination, allele, and haplotype frequencies were analyzed. Associations between the SNPs and EH were explored using multiple linear regression models. Results: Under the dominant model, the -629A allele reduced the odds of having EH (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.34-0.98; p = 0.04), whereas the genotype combination -631CC/-629CC increased the risk of HT (OR = 2.21, 95% CI, 1.23-3.95, p = 0.008). In HT patients, the -629A allele was associated with increased insulin levels (ß = 4.0, 95% CI, 1.21-6.68, p = 0.005), and homeostatic model assessment of insulin resistance (ß = 0.9, 95% CI, 0.17-1.72, p = 0.018), and in NT individuals it was associated with increased high-density lipoprotein cholesterol levels (ß = 3.0, 95% CI, 0.20-5.78, p = 0.036). Conclusion: The CETP -629A allele reduces the odds of having essential arterial hypertension in the Mexican population. Moreover, it exerts a variable effect on diverse biomarkers analyzed in both NT and HT groups.
Assuntos
Proteínas de Transferência de Ésteres de Colesterol/genética , Hipertensão Essencial/genética , Adulto , Alelos , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Hipertensão Essencial/metabolismo , Feminino , Frequência do Gene/genética , Genótipo , Haplótipos/genética , Humanos , Hipertensão/genética , Lipídeos/sangue , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Fatores de RiscoRESUMO
Background: Adiponectin, encoded by the ADIPOQ gene, is produced mainly by adipose tissue, and meaning as a metabolic and immunological regulator. The polymorphism rs822396 in ADIPOQ gene was previously associated with diabetes mellitus type 2, hypertension, and metabolic syndrome components in Caucasian and Asiatic populations. The aim was to evaluate the association of the rs822396 polymorphism of the ADIPOQ gene with anthropometric, clinical, and biochemical alterations related to the metabolic syndrome in the Mexican population. Materials and Methods: Measurements, as well as peripheral blood for DNA extraction, were obtained from 434 participants from Mexico. The rs822396 polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis was made with IBM-SPSSv20. Results: The rs822396G allele frequency was 22.1% in the Mexican population analyzed. In this study were detected differences according to G allele or GG genotype with the highest means, including body mass index (BMI), waist circumference (WC), body fat percentage, visceral fat, systolic arterial tension, glucose levels, triglyceride levels, total cholesterol (TC) levels, very low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase and with triglycerides/glucose index. Significant differences were found with increased risk in the dominant model (AG/GG) of anthropometric, clinical, and biochemical alterations with regard to metabolic syndrome as the BMI [odds ratio (OR) = 2.19], WC (OR = 2.00), waist/hip index (OR = 1.65), body fat percentage (OR = 2.76), visceral fat (OR = 1.84), glucose levels (OR = 1.95), triglyceride levels (OR = 2.75), TC levels (OR = 1.63), high-density lipoprotein (OR = 1.86), and insulin resistance surrogated by the Triglyceride/glucose index (OR = 2.64). Conclusion: The rs822396 polymorphism of the ADIPOQ gene seems to be a risk factor for obesity and metabolic alterations with regard to the metabolic syndrome in the Mexican population.
Assuntos
Adiponectina/genética , Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adiposidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Biomarcadores/sangue , Glicemia , Pressão Sanguínea , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/fisiopatologia , Fenótipo , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Mutations and polymorphisms of the GSK3ß gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3ß rs334558 and rs6438552 polymorphisms with CRC. METHODS: Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. RESULTS: Patients carrying the C/T genotype for the rs334558 (T>C) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05-2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (T>C) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27-0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10-0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3ß (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC. CONCLUSION: Our results denote that GSK3ß gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Glicogênio Sintase Quinase 3 beta/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1ß, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome. METHODS: Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated. RESULTS: Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p <0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p <0.05). CONCLUSIONS: Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.
Assuntos
Índice de Massa Corporal , Frequência do Gene/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Adolescente , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , México , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino). CLINICAL CASE: A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported. CONCLUSIONS: therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.
INTRODUCCIÓN: La acondrogénesis es una displasia esquelética que se caracteriza principalmente por talla baja, micromelia grave, tórax corto y estrecho, prematurez, polihidramnios, hidropesía fetal y muerte fetal in utero o neonatal. Según los hallazgos radiológicos e histopatológicos existen tres tipos de acondrogénesis: tipo 1A (Houston-Harris), tipo 1B (Fraccaro) y tipo 2 (Langer-Saldino). CASO CLÍNICO: Se sometió a estudio a un producto femenino prematuro cuyas características clínicas, radiológicas e histopatológicas fueron compatibles con acondrogénesis tipo 1A. La información familiar permitió concluir que los cuatro productos de los seis embarazos previos se encontraban afectados. El análisis estadístico en por lo menos cuatro familias previamente descritas, incluyendo este caso familiar, mostró diferencias significativas entre el número de miembros esperado y el observado, siendo incongruente con el modo de herencia autosómico recesivo previamente reportado. CONCLUSIONES: Podría considerarse un nuevo subtipo de acondrogénesis tipo 1A debida a la presencia de una mutación germinal preferencial.
Assuntos
Acondroplasia/genética , Acondroplasia/classificação , Feminino , Mutação em Linhagem Germinativa , Humanos , Recém-Nascido , Linhagem , FenótipoRESUMO
El gen de la ataxina-2 es un blanco en la patogénesis de enfermedades complejas, entre ellas los factores de riesgo cardiovascular y enfermedades neurodegenerativas. El gen ATXN2 tiene un VNTR en el exón 1, cuya expansión por encima de las 30 repeticiones provoca al desarrollo de ataxia espinocerebelosa tipo 2; las repeticiones en rango menor se asocian con diabetes tipo 2 o esclerosis lateral amiotrófica. También este locus está ligado con fenotipos metabólicos e inflamatorios. En conclusión, el gen puede ser utilizado como marcador clínico de fenotipos metabólicos y neurológicos, lo cual está relacionado con su efecto pleiotrópico.
The ataxin 2 gene is a target in the pathogenesis of complex diseases, including cardiovascular risk factors and neurodegenerative diseases. ATXN2 gen has VNTR in exon 1, whose expansion exceeding 30 repetitions leads to the development of spinocerebellar ataxia type 2; lower-range repetitions are associated with type 2 diabetes or amyotrophic lateral sclerosis. This locus is also linked with metabolic and inflammatory phenotypes. In conclusion, this gene can be used as a clinical marker of metabolic and neurological phenotypes, which is related to its pleiotropic effect.
Assuntos
Ataxina-2/genética , Doenças Cardiovasculares/genética , Doenças Neurodegenerativas/genética , Biomarcadores/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Doenças Neurodegenerativas/fisiopatologiaRESUMO
Resumen El gen de la ataxina-2 es un blanco en la patogénesis de enfermedades complejas, entre ellas los factores de riesgo cardiovascular y enfermedades neurodegenerativas. El gen ATXN2 tiene un VNTR en el exón 1, cuya expansión por encima de las 30 repeticiones provoca al desarrollo de ataxia espinocerebelosa tipo 2; las repeticiones en rango menor se asocian con diabetes tipo 2 o esclerosis lateral amiotrófica. También este locus está ligado con fenotipos metabólicos e inflamatorios. En conclusión, el gen puede ser utilizado como marcador clínico de fenotipos metabólicos y neurológicos, lo cual está relacionado con su efecto pleiotrópico.
Abstract The ataxin 2 gene is a target in the pathogenesis of complex diseases, including cardiovascular risk factors and neurodegenerative diseases. ATXN2 gen has VNTR in exon 1, whose expansion exceeding 30 repetitions leads to the development of spinocerebellar ataxia type 2; lower-range repetitions are associated with type 2 diabetes or amyotrophic lateral sclerosis. This locus is also linked with metabolic and inflammatory phenotypes. In conclusion, this gene can be used as a clinical marker of metabolic and neurological phenotypes, which is related to its pleiotropic effect.
Assuntos
Humanos , Doenças Cardiovasculares/genética , Doenças Neurodegenerativas/genética , Ataxina-2/genética , Biomarcadores/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/genéticaRESUMO
The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t-test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsamiR4325p (pâ¯<â¯0.05). We also found upregulation of hsamiR1945p (pâ¯<â¯0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsamiR4325p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsamiR4325p and hsamiR1945p are associated with the regulation of proinflammatory pathways and RA flare-up.
Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/genética , MicroRNAs/sangue , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , RecidivaRESUMO
Background: Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino). Clinical case: A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported. Conclusions: therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.
Introducción: La acondrogénesis es una displasia esquelética que se caracteriza principalmente por talla baja, micromelia grave, tórax corto y estrecho, prematurez, polihidramnios, hidropesía fetal y muerte fetal in utero o neonatal. Según los hallazgos radiológicos e histopatológicos existen tres tipos de acondrogénesis: tipo 1A (Houston-Harris), tipo 1B (Fraccaro) y tipo 2 (Langer-Saldino). Caso clínico: Se sometió a estudio a un producto femenino prematuro cuyas características clínicas, radiológicas e histopatológicas fueron compatibles con acondrogénesis tipo 1A. La información familiar permitió concluir que los cuatro productos de los seis embarazos previos se encontraban afectados. El análisis estadístico en por lo menos cuatro familias previamente descritas, incluyendo este caso familiar, mostró diferencias significativas entre el número de miembros esperado y el observado, siendo incongruente con el modo de herencia autosómico recesivo previamente reportado. Conclusiones: Podría considerarse un nuevo subtipo de acondrogénesis tipo 1A debida a la presencia de una mutación germinal preferencial.
Assuntos
Acondroplasia/classificação , Doenças do Prematuro/classificação , Anormalidades Múltiplas/genética , Acondroplasia/diagnóstico por imagem , Acondroplasia/genética , Acondroplasia/patologia , Cartilagem/patologia , Evolução Fatal , Feminino , Fêmur/patologia , Mutação em Linhagem Germinativa , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/genética , Doenças do Prematuro/patologia , Linhagem , Fenótipo , Poli-Hidrâmnios/etiologia , GravidezRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in adolescents, is a feature of metabolic syndrome (MetS). Obesity and insulin resistance (IR) are risk factors for NAFLD, as well as inflammation-related genetic markers. The relationship between metabolic or inflammation-related genetic markers and alanine aminotransferase (ALT) is not fully understood. We examined the relationship of MetS, metabolic and inflammation-related genetic markers with elevated ALT in adolescents. METHODS: A total of 674 adolescents participated in a cross-sectional study in Guadalajara, Mexico. Elevated ALT (>40 IU/L), a surrogate marker of NAFLD, and MetS (International Diabetes Federation definition) were evaluated. Obesity, IR, lipids, C-reactive protein (CRP) and genetic markers (TNFA-308G>A, CRP+1444C>T, IL1RN and IL6-597/-572/-174 haplotype) were evaluated. Multivariate logistic regression was performed. RESULTS: Elevated ALT was observed in 3% and 14.1% (total and obese, respectively) of the adolescents. Obesity (odds ratio [OR], 5.86; 95% confidence interval [95% CI], 1.16-25.89), insulin (OR, 8.51; 95% CI, 2.61-27.71), IR (OR, 9.10; 95% CI, 2.82-29.38), total cholesterol (TC) (OR, 3.67; 95% CI, 1.25-10.72), low-density lipoprotein-cholesterol (LDL-C) (OR, 3.06; 95% CI, 1.06-8.33), non-high-density lipoprotein-cholesterol (HDL-C) (OR, 3.88; 95% CI, 1.27-11.90) and IL1RN (OR, 4.64; 95% CI, 1.10-19.53) were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT (OR, 4.22; 95% CI, 1.14-15.71). CONCLUSIONS: Obesity, insulin, IR, high TC, high LDL-C, high non-HDL-C and IL1RN polymorphism were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT. There is an urgent need to reduce obesity and IR in adolescents to prevent NAFLD.
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Alanina Transaminase/metabolismo , Marcadores Genéticos , Resistência à Insulina , Síndrome Metabólica/diagnóstico , Obesidade/complicações , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , México/epidemiologia , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays. The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.
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Calpaína/genética , Diabetes Gestacional/genética , Mutação INDEL , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Glicemia/análise , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Feminino , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , México , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Several studies have shown a strong association between diabetes mellitus (DM) and increased risk of colorectal cancer (CRC). The fundamental mechanisms that support this association are not entirely understood; however, it is believed that hyperinsulinemia and hyperglycemia may be involved. Some proposed mechanisms include upregulation of mitogenic signaling pathways like MAPK, PI3K, mTOR, and WNT, which are involved in cell proliferation, growth, and cancer cell survival. The purpose of this study was to evaluate the gene expression profile and identify differently expressed genes involved in mitogenic pathways in CRC patients with and without DM. METHODS: In this study, microarray analysis of gene expression followed by quantitative PCR (qPCR) was performed in cancer tissue from CRC patients with and without DM to identify the gene expression profiles and validate the differently expressed genes. RESULTS: Among the study groups, some differently expressed genes were identified. However, when bioinformatics clustering tools were used, a significant modulation of genes involved in the WNT pathway was evident. Therefore, we focused on genes participating in this pathway, such as WNT3A, LRP6, TCF7L2, and FRA-1. Validation of the expression levels of those genes by qPCR showed that CRC patients without type 2 diabetes mellitus (T2DM) expressed significantly more WNT3Ay LRP6, but less TCF7L2 and FRA-1 compared to controls, while in CRC patients with DM the expression levels of WNT3A, LRP6, TCF7L2, and FRA-1 were significantly higher compared to controls. CONCLUSIONS: Our results suggest that WNT/ß-catenin pathway is upregulated in patients with CRC and DM, demonstrating its importance and involvement in both pathologies.
Assuntos
Neoplasias Colorretais/genética , Diabetes Mellitus Tipo 2/genética , Via de Sinalização Wnt/fisiologia , beta Catenina/genética , Idoso , Neoplasias Colorretais/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The MDM2 gene plays an important role in tumorigenesis. The data on the Del1518 promoter polymorphism in the MDM2 gene have revealed associations with cancer. MATERIAL AND METHODS: We examined the role of the MDM2 Del1518 polymorphism through a comparison of the genotypes of 345 healthy Mexican women with those of 742 Mexican women with breast cancer (BC). RESULTS: The genotype frequencies of the MDM2 Del1518 polymorphism in controls and patients with BC were 64% and 55.5% for ins/ins, 32% and 31.5% for ins/del, and 4% and 13% for del/del, respectively. The obtained odds ratio (OR) was 3.26, with a 95% confidence interval (95% CI) of 1.86-5.72 and p=0.0001, for the del/del genotype. An association was evident when we examined the distribution of the del/del genotype in patients with elevated levels of transaminase SGPT (OR=2.268; 95% CI=1.40-3.65; p=0.0001). Additionally, we observed an association of the genotypes del/del - ins/del in menopausal patients with BC with the following characteristics: tobacco consumption (OR = 1.93, 95% CI = 1.07-3.4, p=0.025), pregnancy loss (OR=2.44, 95% CI=1.37-4.35, p=0.0024), obesity (I-IV) (OR=1.8, 95% CI=1.1-2.9, p= 0.018), and elevated serum glucose levels (OR=3.72, 95% CI=2.0-6.85, p=0.0001). CONCLUSIONS: The MDM2 Del1518 polymorphism was associated with BC susceptibility, particularly in menopausal patients with BC who reported tobacco consumption, pregnancy loss, obesity and high glucose levels in the analyzed Mexican population.
Assuntos
Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Aborto Espontâneo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Menopausa/genética , México , Pessoa de Meia-Idade , Gravidez , Regiões Promotoras GenéticasRESUMO
OBJECTIVES: To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. METHODS: A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians - an Amerindian group from southeastern Mexico - were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F-statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. RESULTS: Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. CONCLUSIONS: The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country.