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.
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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.
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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.
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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.