Association Of C677T Polymorphism Research Articles

ASSOCIATION OF C677T POLYMORPHISMS OF MTHFR GENE WITH RECURRENT PREGNANCY LOSS IN VIETNAMESE WOMAN

Background: Recurrent pregnancy loss is a major concern in gynecology. Recently, many papers have showed the role of genetic factors in etiology of recurrent pregnancy loss. Several published studied revealed that C677T polymorphism is a high risk of recurrent pregnancy loss. However, this finding is still controversy. Therefore, this study is aimed at investigating the association of C677T polymorphisms of MTHFR gene with recurrent pregnancy loss in Vietnamese woman. Methods: Study subjects comprised 100 healthy women (control group) and 52 women with recurrent pregnancy loss. C677T polymorphisms were identified by PCR-technique. Results: The frequency of 677CC, 677CT, and 677TT genotypes in Vietnamese women with recurrent pregnancy loss is 65.4%, 30.8%, 3.8%, respectively; while the distribution of those genotypes in the control-group is 86%, 12%, và 2% (χ2 = 8.83; p = 0.012). Statistic analysis revealed that MTHFR C677T polymorphismsare associated with recurrent pregnancy loss (for CT vs. CC: OR= 3.37, 95%CI: 1.44 – 7.87, p = 0.0049; for (677CT + 677TT) vs. CC: OR= 3.25, 95%CI: 1.46 – 7.26, p = 0.004; for T vs. C: OR= 2.74, 95%CI:1.55 – 5.55, p = 0.005). Key words: Recurrent pregnancy loss, C677T polymorphisms, MTHFR gene

The C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and Susceptibility to Late-onset Alzheimer's Disease.

Folate metabolism makes a crucial contribution towards late-onset Alzheimer’s disease (LOAD). Moreover, methylenetetrahydrofolate reductase (MTHFR) constitutes the primary enzyme of the folate pathway. We hypothesize that there is an association of C677T polymorphism in the MTHFR gene with the susceptibility to LOAD. Previous published research has investigated the link between the MTHFR C677T polymorphisms and LOAD susceptibility; nevertheless, the findings have continued to be not only controversial, but also indecisive. Accordingly, we carried out the present meta-analysis for the assessment of the potential link that exists between the MTHFR C677T polymorphism and the susceptibility to LOAD. Furthermore, we carried out a literature search of the PubMed, EMBASE, Cochrane Library, and WanFang database up to August 10, 2018. The odds ratios (ORs) with the respective 95% confidence interval (95%CI) were put to use for the evaluation of the robustness of the link of the MTHFR C677T polymorphism with the vulnerability to LOAD. All statistical analyses were carried out using STATA 15.0. An aggregate of 14 case-control research works was retrieved, involving 2,467 LOAD patients as well as 2,877 controls. We found that a substantial link exists between C677T polymorphism and LOAD risk in a codominant framework (TC vs. CC: OR=1.22, 95%CI=1.00-1.49, P=0.049). In addition to the stratified analysis based on ethnicity, which suggested that C677T polymorphism was likely linked only to an augmented threat of LOAD in Asians, it did not exist among Caucasians. Furthermore, in the subgroup analysis carried out using APOE ɛ4 status, a substantial increase in the susceptibility to LOAD was detected in APOE ɛ4 carriers as well as non-APOE ɛ4 carriers. In sum, the current meta-analysis revealed that MTHFR C677T polymorphism was associated with susceptibility to LOAD. Further extensive case-control studies are required.

Association of C677T polymorphism (rs1801133) in MTHFR gene with depression.

Depression is one of the mental disorders with a state of low mood and aversion to activities that exerts a negative effect on a person's thoughts and behavior. Genetic association studies on MTHFR C677T polymorphism and depression have been repeatedly performed over the last two decades, but results are inconsistent. The aim of the present study was to assess the relationship between MTHFR C677T polymorphism and depression by literature review and meta-analysis. Four electronic databases, PubMed, Google Scholar, Science direct and Springer Link were searched for case control articles focusing on MTHFR C677T polymorphism and the risk of depression. A total of 30 studies including 4,802 cases and 17,362 controls were involved in present meta-analysis. When all the eligible studies were pooled into this meta-analysis, significant association between depression risk and MTHFR C677T polymorphism was found in three genetic models (Additive model: OR T vs C= 1.20, 95 % CI= 1.00-1.34, p=0.0004; homozygote model: OR TT vs.CC=1.37, 95% CI= 1.13-1.65, p=0.0004; dominant model: OR TT+CT vs CC=1.13, 95 % CI= 0.99-1.28, p=0.04), while meta-analysis with other two genetic models did not show association with other two genetic models ( recessive model: OR TT vs CT+CC= 1.36, 95 % CI = 0.91-2.04, p=0.13; co-dominant model: OR CT vs CC=1.00, 95 % CI=0.93-1.08,p=0.84). Present meta-analysis supports that there is a meager significant association between MTHFR C677T polymorphism and depression risk.

Associations of C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene with male infertility risk: A meta-analysis

PurposeMethylenetetrahydrofolate reductase is one of the key enzymes in folate metabolism. But the association between polymorphism and the risk of male infertility is still controversial. Therefore, this study used a meta-analysis on the collection of data to analyze MTHFR gene C677T polymorphism (known as c.665 C>T, rs1801133, p.Ala222Val). MethodsPubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan fang. Data were searched to identify eligible studies. We sifted the data collection by Hardy-Weinberg equilibrium calculator and used odds ratios (ORs) and 95% confidence intervals (95% CIs) to conduct data through RevMan5.0 and StataSE12.0 software. ResultsA total of 15 studies have 3853 patients with infertility and 3613 healthy controls in this meta-analysis. Our results showed that T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of male infertility (forT vs. C: OR=1.38, 95% CI=1.18–1.63; for TT vs. CC: OR=1.86, 95% CI=1.36–2.54; for CT vs. CC: OR=1.34, 95% CI=1.03–1.74; for TT vs. CT: OR=1.52, 95% CI=1.26–1.84; for TT vs. CT+CC: OR=1.42, 95% CI=1.19–1.70; for TT+CT versus CC: OR=1.46, 95%CI=1.05–2.04). In addition, the results indicated that T allele had the positive association which was driven by East-asian populations (random: OR=1.44, 95% CI=1.2–1.74; fixed: OR=1.39, 95% CI=1.20–1.61), Middle-eastern populations (random: OR=1.30, 95% CI=1.05–1.63; fixed: OR=1.30, 95% CI=1.05–1.63) and Mixed-race (random: OR=1.96, 95% CI=1.35–2.85; fixed: OR=1.31, 95% CI=1.20–1.43). ConclusionThis meta-analysis suggests that MTHFR C677T polymorphism is associated with male infertility.

Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies

BackgroundMethylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs.MethodsAn electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis.ResultsA significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls.ConclusionThe results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted.

Polymorphisms of MTHFR C677T and A1298C Association With Oral Carcinoma Risk: A Meta-Analysis

Investigations regarding association of MTHFR polymorphisms with oral carcinoma risk have yielded inconclusive results. Thus, meta-analyses were performed. Results showed that no associations of C677T polymorphisms with oral carcinoma were observed for the overall data. In subgroup analyses by drinking status, homozygous TT alleles exhibited elevated oral cancer susceptibility in heavy drinkers. For A1298C polymorphism, CC alleles presented a possible preventive role for oral cancer. Collectively, results suggest that MTHFR 677TT polymorphism might be a low-penetrant risk factor for oral carcinoma only in heavy drinkers. Conversely, 1298CC alleles might play a preventive role for oral cancer.

C677T Polymorphism of the 5,10 MTHFR Gene in Young Mexican Subjects with ST-Elevation Myocardial Infarction

The C677T polymorphism of 5,10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with hypertension and coronary artery disease in several populations worldwide, but results are still controversial. The aim of this study was to examine the possible association of C677T polymorphism with ST-elevation myocardial infarction (STEMI) in young Mexican subjects. In a case-control study, 167 unrelated patients < or = 45 years of age with diagnosis of STEMI who were admitted to a cardiovascular intense care unit and 167 unrelated controls subjects matched by age and gender were recruited from January 2006 and June 2009. The C677T polymorphism was determined in all participants by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). There was no significant difference in the genotype distribution between groups (p = 0.69) or allele frequency (p = 0.40). There were independent factors for STEMI: smoking (OR 4.9, 95% CI 3.0-8.1, p = 0.001), hypertension (OR 1.8, 95% CI 1.0-3.3, p = 0.03), family history of atherothrombotic disease (OR 2.3, 95% CI 2.0-4.6, p = 0.02), and dyslipidemia (OR 3.2, 95% CI 1.8-5.6, p <0.001). Diabetes mellitus did not represent an independent risk factor for STEMI (OR 1.2, 95% CI 0.2-2.2, p = 0.82). The TT genotype from the C677T of 5,10 MTHFR gene is not an independent risk factor for STEMI in the Mexican population. However, more studies are needed to determine the possible "protective effect" of the C677T polymorphism in our population.

ApoA-I

See related article, pages 564–571 A link between homocysteine and atherothrombotic vascular disease was first suggested by McCully more than 30 years ago.1 The vascular lesions observed by McCully in children with inborn errors of homocysteine metabolism were fibrotic rather than lipid rich, suggesting the possibility that hyperhomocysteinemia may produce vascular pathology through a mechanism independent of altered lipid metabolism. Since that time, many epidemiological studies have confirmed that elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of coronary events, stroke, and venous thromboembolism.2–4 Most of the epidemiological data indicate that elevation of plasma tHcy is not associated with a significant change in plasma total cholesterol but is negatively associated with high density lipoprotein (HDL) cholesterol.5–7 An effect of homocysteine on HDL metabolism could be clinically important, because HDL protects from vascular disease not only by facilitating reverse cholesterol transport8 but also through its direct antiinflammatory properties.9 During the past decade, the development of animal models has led to rapid progress in defining the pathophysiological consequences of hyperhomocysteinemia in vivo. Experimental approaches to induce hyperhomocysteinemia in animals include the use of diets that are high in methionine and/or low in folate, as well as genetic approaches, such as the generation of knockout mice with targeted disruption of the cystathionine β-synthase ( Cbs ),10 methylene tetrahydrofolate reductase ( Mthfr ),11 or methionine synthase ( Mtr )12 genes. Like hyperhomocysteinemic humans, hyperhomocysteinemic animals develop endothelial dysfunction, hepatic lipid accumulation, and decreased plasma HDL cholesterol with minimal changes in plasma …

Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis.

To evaluate whether the C677T polymorphism of the methylenetetrahydofolate reductase (MTHFR) gene is consistently associated with hypertension in pregnancy. Meta-analysis of studies comparing women with and without hypertension in pregnancy for the C677T MTHFR polymorphism. Studies were identified with MEDLINE and EMBASE searches complemented with perusal of bibliographies of retrieved articles and communication with investigators. Between-study heterogeneity was estimated and data were combined with random effects models. Sensitivity analyses examined the effect of population and disease characteristics. Bias diagnostics evaluated the evolution of the postulated genetic effect over time and the potential for publication bias. Across 23 comparisons (3169 hypertensive women, 3044 controls), having the T allele (TT or CT) increased the odds of hypertensive disease of pregnancy by 1.21-fold (95% confidence interval, 1.01-1.44), but there was large between-study heterogeneity (P = 0.003). The results were similar and heterogeneity persisted when sensitivity analyses were limited to studies of Caucasian populations, or those of patients with significant proteinuria. While patients with diastolic hypertension > or = 110 mmHg showed an odds ratio of 1.41 (95% confidence interval, 1.03-1.73), no association was seen in patients with less severe diastolic hypertension (odds ratio, 1.00; 95% confidence interval, 0.61-1.65). Early published studies tended to show stronger associations than the subsequent studies. While bias cannot be excluded, the meta-analysis suggests that the T allele may increase the risk of severe diastolic hypertension during pregnancy.