Risk of Down syndrome conferred by MTHFR C677T polymorphism: Ethnic variations.
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ABSTRACT:
SUBMITTER: Dutta S
PROVIDER: S-EPMC3168164 | biostudies-literature | 2007 May
REPOSITORIES: biostudies-literature
Publications
Risk of Down syndrome conferred by MTHFR C677T polymorphism: Ethnic variations.
Dutta Samikshan S Das Aneek Bhowmik AB Mukhopadhyay Kanchan K
Indian journal of human genetics 20070501 2
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Project description:Definition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis. A total of 176 CSX patients and 196 healthy subjects with similar age and clinical features were compared in terms of C677T polymorphism of the MTHFR gene. There was no significant difference in terms of MTHFR gene C677T polymorphism between CSX patients and controls. When genotypic distribution was compared based on gender in both patients and controls, no significant difference was found between male and female subjects (P>.05). As fasting blood sugar and urea values were significantly higher, alanine aminotransferase and gamma-glutamyl transferase levels were significantly lower in the patients than the controls (P<.05). Described family story of the patients was significantly higher than the controls (P<.05). These suggest that homocysteine metabolism in CSX is not directly related to the endothelial dysfunction and thus the effect on the microvascular circulation.
| S-EPMC6817037 | biostudies-literature
Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were found associated with body mass index (BMI)-defined obesity and lean mass. The aim of our study was to examine the role of the C677T MTHFR gene polymorphism in the response to diet in the management of metabolic syndrome. We investigated the body composition and metabolic factor changes after an hysocaloric balanced diet (HBD), in Italian obese women affected by metabolic syndrome (MS).MethodsForty four obese women affected by MS were eligible for the study. A HBD for 12 weeks was assigned. Study participation included a complete screening for dietary habits, anthropometry, body composition, blood biochemical markers and C677T MTHFR polymorphism genotyping. The study has been registrated by ClinicalTrials.gov Id: NCT01890070.ResultsThe highest number of responders to HBD nutritional intervention were T(-) carriers (p ≤ 0.05). In the 81% of the total population a loss of Total Body Lean was observed. A significative loss (p ≤ 0.05) of Total Body Lean was observed in the 47% of T(-) carriers and in the 53% of T(+) carriers. Diastolic and systolic blood pressure, and waist circumference were reduced (p ≤ 0.05). The prevalence of MS parameters decreased by 84% for systolic and diastolic blood pressure; 79,5% for HDL cholesterol, 82% for fasting glucose and 77% for triglycerides.ConclusionsMTHFR genetic variations analysis would be an innovative tool for the nutritional assessment. Our data provide the basis for personalized dietary recommendations based on the individual's genetic makeup and nutritional status.Trial registrationThe study has been registrated by ClinicalTrials.gov Id: NCT01890070.
| S-EPMC4260200 | biostudies-literature
Project description:Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%), but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism.
| S-EPMC4241316 | biostudies-literature
Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.AimA meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.MethodsPubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment.ResultsThirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR?=?1.26, 95% CI?=?1.09-1.46, p?=?0.001; for TT vs. CC, OR?=?1.49, 95% CI?=?1.13-1.97, p?=?0.008; for CT vs. CC, OR?=?1.29, 95% CI?=?1.10-1.51, p?=?0.001; for TT+CT vs. CC, OR?=?1.35, 95% CI?=?1.13-1.60, p?=?0.0008; for TT vs. CT+CC, OR?=?0.76, 95% CI?=?0.60-0.94, p?=?0.01).ConclusionThe results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.
| S-EPMC4180743 | biostudies-literature
Project description:MTHFR C677T polymorphism has been indicated to be a risk factor for cancers, but its association with head and neck cancer (HNC) risk remains inconclusive. In the present study, we aimed to get a more precise estimation by performing a quantitative meta-analysis. Published papers up to Jun 2014 was searched and screened. Necessary information was rigorously extracted for data pooling and analyzing, and then, subgroup analyses on ethnicity, source of controls, sample size, tumor type, smoking and drinking status were also carried out. As a result, twenty-three case-control studies including 14298 subjects were included. The overall data failed to reveal a significant association between MTHFR C677T polymorphism and HNC risk (homozygote comparison model: OR = 1.16; 95%CI = 0.93-1.45; dominant model: OR = 1.05; 95%CI = .90-1.21; recessive model: OR = 1.14; 95%CI = 0.93-1.38). However, in the subgroup analysis about drinking status, increase risk was shown in the heavy drinking subgroup (TT vs CC: OR = 3.11; 95%CI = 1.52-3.02). In conclusion, the results of the present study suggest that Homozygous TT alleles of MTHFR C677T polymorphism might be a risk factor for HNC among individuals who have a heavy drinking history. Further studies are needed to get a more definitive conclusion.
| S-EPMC4451849 | biostudies-other
Project description:Objective: For analyzing the distribution characteristics of MTHFR C677T polymorphism in Chinese females in order to provide information for reducing birth defects and formulating public health policies to prevent congenital malformations. Methods: Literature search in the last 6 years on "MTHFR C677T," "polymorphism" and "methylene tetrahydrofolate reductase." The included literature provides the MTHFR C677T frequency in healthy females in the corresponding regions. The data were grouped by the national administrative region as a unit to obtain the distribution information of the MTHFR C677T and alleles in the female population in every province, municipality or autonomous region. This was done for analyzing the overall distribution of the MTHFR C677T allele and the geographical distribution of pregnancy complications. Results: A total of 126 studies were included, covering five autonomous areas, four municipalities directly under the Central Government, as well as 22 provinces (except Taiwan Province) in China. MTHFR C677T polymorphism data of 27 groups of Chinese Han women and 31 groups of other Chinese females were obtained, and the chi-square test revealed notable inter-group differences (p = 0.000). The TT genotype and T allele of MTHFR C677T accounted for 18.2% (4.7%-38.3%) and 40.3% (19.7%-61.4%) of the Chinese female population, respectively, with a significant north-south difference. Chinese females had a consistent frequency of the T allele with the geographical distribution of pregnancy complications such as recurrent abortion and preeclampsia. Conclusion: With a obvious geographical gradient, the MTHFR C677T polymorphism distribution in Chinese females is consistent with the geographical distribution of multiple pregnancy complications, and the risk assessment for it might be included in primary prevention for birth defects.
| S-EPMC10160643 | biostudies-literature
Project description:IntroductionAbnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy.ObjectiveTo establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals.MethodsData from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics(®)). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed.ResultsMicroarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001).ConclusionsResults for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies.
| S-EPMC4536819 | biostudies-literature
Project description:BackgroundAssociation between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme involved in folate metabolism and DNA methylation, and breast cancer risk are inconsistent. We investigated in a case-control study, possible effect of the common MTHFR C677T polymorphism on breast cancer risk in a sample of Iranian patients.Materials and methodsThe study subjects comprised of 123 breast cancer cases and 110 cancer-free control, who were matched for age and body mass index (BMI). C677T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Lipid profile was measured in all subjects by standard method.ResultsThe genotypes distributions (CC, CT, and TT) were 55.3, 39, and 5.7% in breast cancer cases and 51.8, 44.5, and 3.6% in controls. Chi square analysis revealed that there was no significant association between breast cancer risk and MTHFR genotypes and alleles. Additionally, no significant association was observed between C677T genotypes and biochemistry parameters. A multinomial logistic regression model with MTHFR genotypes, lipid profiles, BMI and age as covariates revealed that there is no significant association between MTHFR genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.ConclusionsOur findings do not support the hypothesis that genetic variation in the MTHFR C677T polymorphism is implicated in the breast cancer risk in a sample of Iranian patients.
| S-EPMC4785787 | biostudies-literature
Project description:BackgroundDown syndrome (DS) is one of the most common chromosomal abnormalities among live-born babies and one of the best-known intellectual disability disorders in humans. Errors leading to trisomy 21 are primarily arising from defects in chromosomal segregation during maternal meiosis (about 88% of cases), and the focus of many investigations has been to identify maternal risk factors favoring chromosome 21 malsegregation during oogenesis. Maternal polymorphisms of genes required for folate metabolism are the most investigated risk factors for the birth of children with DS. Through this review, we sought to investigate the association of the polymorphisms "C677T" and "A1298C" of the MTHFR gene with maternal risk for DS.MethodsWe will use the databases PubMed, Embase, Scopus and Web of Science to search for case-control studies published from 1999 up to September 2021 without language restriction. Results will be presented as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. The all data synthesis will be analyzed on the Review Manager 5.2 version software.ResultsThis study will be able to clarify all the doubts we seek and that it will be able to provide accurate data that will be able to describe how these polymorphisms can act to increase the predisposition for the birth of children with DS in different populations and under different dietary conditions.ConclusionsThis study will clarify the relationship between C677T and A1298C polymorphisms MTHFR gene with increased the maternal risk for Down syndrome.RegistrationThis systematic review and meta-analysis protocol has been registered on the Prospective Registry of International Systematic Review and Meta-analyses: CRD42021269338.
| S-EPMC8772651 | biostudies-literature
Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR) is an important enzyme for folate metabolism in humans; it is encoded by the MTHFR gene. Several studies have assessed the association between MTHFR C677T polymorphism and the risk of congenital heart defects (CHDs), while the results were inconsistent.Methods and findingsMultiple electronic databases were searched to identify relevant studies published up to July 22, 2012. Data from case-control and TDT studies were integrated in an allelic model using the Catmap and Metafor software. Twenty-nine publications were included in this meta-analysis. The overall meta-analysis showed significant association between MTHFR C677T polymorphism and CHDs risk in children with heterogeneity (P heterogeneity = 0.000) and publication bias (P egger = 0.039), but it turned into null after the trim-and-fill method was implemented (OR = 1.12, 95% CI = 0.95-1.31). Nevertheless, positive results were obtained after stratified by ethnicity and sample size in all subgroups except the mixed population. For mothers, there was significant association between the variant and CHDs without heterogeneity (P heterogeneity = 0.150, OR = 1.16, 95% CI = 1.05-1.29) and publication bias (P egger = 0.981). However, the results varied across each subgroup in the stratified analysis of ethnicity and sample size.ConclusionsBoth infant and maternal MTHFR C677T polymorphisms may contribute to the risk of CHDs.
| S-EPMC3594197 | biostudies-literature