Association Of Methylenetetrahydrofolate Reductase C677T Polymorphism Research Articles

Biochemical Association of MTHFR C677T Polymorphism with Myocardial Infarction in the Presence of Diabetes Mellitus as a Risk Factor.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.

Effect of methylenetetrahydrofolate reductase C677T polymorphism on serum folate but not vitamin B12 levels in patients with H-type hypertension.

Hyperhomocysteinemia (HHcy) is a common complication in Chinese hypertensive patients and associated with methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, folate, and vitamin B12 (Vit B12) status. This study evaluated the associations of MTHFR C677T polymorphism, folate, and Vit B12 with H-type hypertension. 887 eligible patients with essential hypertension were included. Patients were divided into two groups according to the Hcy level, the H-type hypertension group and the normal hypertension group. Related risk factors such as MTHFR polymorphism, folate and Vit B12 status were analyzed in the two groups. Age, gender, SBP, DBP, MTHFR C677T genotype, folate and Vit B12 differed significantly between H-type hypertension and normal hypertension groups (P < 0.05). MTHFR 677TT variant, gender, folate, and Vit B12 were independent risk factors for the occurrence of H-type hypertension. The risk for TT carriers was 8 times higher than that of CC and CT carriers [OR (95% CI) 8.248 (5.274-12.899)]. Male patients had almost fivefold higher odds than female patients [OR (95% CI) 4.923 (2.741-8.842)]. Folate level of patients with H-type hypertension decreased with the C to T substitution of MTFHR C677T gene (P < 0.05), while Vit B12 level was not associated with the gene (P > 0.05). MTHFR 677TT variant, gender, folate, and Vit B12 were risk factors for the occurrence of H-type hypertension. Folate but not Vit B12 was associated with MTFHR C677T polymorphism in patients with H-type hypertension. Accordingly, the above factors may be considered in the prevention and treatment of hypertension.

Association of MTHFR C677T polymorphism with primary open angle glaucoma: a Meta-analysis based on 18 case-control studies.

To systematically understand the genetic association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and primary open angle glaucoma (POAG). A comprehensive literature search in Google Scholar, PubMed, Science Citation Index, Foreign Medical Literature Retrieval Service, Chinese National Knowledge Infrastructure and Wanfang Databases was performed to collect all eligible studies up to August 2019. Study selection, data abstraction and study quality evaluation were performed by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. Eighteen case-control studies including 2156 cases and 2201 controls were identified. There was no significant difference in the terms of MTHFR C677T polymorphism and POAG in the Caucasian population (for T vs C OR=1.11, 95%CI: 0.88 to 1.39; for TT vs CC OR=1.01, 95%CI: 0.76 to 1.36; for TT+TC vs CC OR=1.15, 95%CI: 0.84 to 1.58 and for TT vs TC+CC OR=1.02, 95%CI: 0.78 to 1.33). However, a significant effect was revealed in the Asian population (for T vs C OR=1.34, 95%CI: 1.12 to 1.59; for TT+TC vs CC OR=1.41, 95%CI: 1.14 to 1.76). Based on 18 eligible studies, we provide a correlation between MTHFR C677T polymorphism and POAG among the Asians subgroup indicating that the T allele or TT +TC genotype may play a critical role in POAG development in Asians.

Association of MTHFR C677T Polymorphism With Antipsychotic-Induced Change of Weight and Metabolism Index.

Although antipsychotic medication contributed to the improvement of psychotic symptoms and reduced relapse, it induced weight gain and metabolic syndrome during antipsychotic medication treatment, which was seriously concerning. To investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T (rs1801133) polymorphism with antipsychotic-induced weight gain and metabolism parameter change, we employed 1,868 patients with schizophrenia in this study and randomly allocated them to seven antipsychotic medication treatment groups. All patients received antipsychotics monotherapy and were followed up for 6 weeks. Height, body weight, and metabolic parameters of the patients were measured at baseline and at 2, 4, and 6 weeks after antipsychotic treatment. We genotyped blood DNA from patients for MTHFR C677T polymorphisms and performed quantitative analyses using analysis of variance (ANOVA) and the analysis of covariance (ANCOVA) among three genotype groups.We found a predominant association between MTHFR C677T and body weight mass index (BMI) change after 6-week risperidone treatment. After 6-week treatment of risperidone, the BMI change rate (%) of MTHFR C677 carriers was significantly higher than that of MTHFR TT genotype carriers [CC (2.81 ± 6.77)%, CT (3.79 ± 5.22)%, TT (1.42 ± 3.53)%, F = 4.749, P = 0.009]. Some of the abnormal metabolic parameters were found to be associated with the MTHFR 677T, including higher levels of low-density lipoprotein and waist circumference. Validation was performed in an independent cohort, consisting of 252 patients with schizophrenia treated with three atypical antipsychotic drugs. Overall, the MTHFR C677 was associated with high risk of antipsychotic-induced weight gain and metabolism abnormalities.

Association of MTHFR C677T polymorphism with severity and localization of chronic atrophic gastritis patients without Helicobacter pylori infection: a case control study

BackgroundPrevious reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains ambiguous. We aimed to determine the possible relationship between MTHFR C677T polymorphism and the severity of atrophic gastritis.MethodsA total of 128 patients without Helicobacter pylori infection were included in the study. The severity of gastric atrophy was assessed by pathological diagnosis using OLGA and OLGIM Gastritis Staging System. MTHFR 677C > T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test.ResultsIn this study, the TT genotype was significantly more frequent among Helicobacter pylori-negative patients aged ≤44 years (age ≤ 44 years vs. > 44 years, P = 0.039). Patients with TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC + CT, P = 0.02). Furthermore, TT genotype was associated with more severe lesions compared with the CC + CT genotypes (TT vs. CC + CT for atrophy: P = 0.07; for intestinal metaplasia: P = 0.01; for moderate-to-severe lesions: P = 0.01). OLGA and OLGIM stages III-IV were observed more frequently in patients with TT genotype compared with CC + CT genotypes (for OLGA: P = 0.003; for OLGIM: P = 0.036).ConclusionsThe MTHFR 677C > T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results indicate that MTHFR C677T polymorphism may act as a predictive marker for precancerous gastric lesions, especially in Helicobacter pylori-negative patients aged ≤44 years.

MTHFR C677T Polymorphism and risk of nonsyndromic cleft in craniofacial region in a South Indian Population

Introduction: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was found associated with cleft palate (CP) and cleft lip with or without CP in different populations and only very few studies were conducted in the Indian population. The aim of this case–control study is to detect whether there is any association of C677T MTHFR gene polymorphism with clefts in the craniofacial region, especially with Nonsyndromic cleft lip with cleft palate (NSCLP) in the South Indian population. Material and Methods: The study was conducted on 179 nonsyndromic cleft cases and 130 healthy individuals without cleft were included as controls. To detect the polymorphism, polymerase chain reaction–restriction fragment length polymorphism method was carried out, and the result was analyzed using Chi-square test and binary logistic regression model. Results: Among the cleft cases, 120 were NSCLP and it showed 6.67% CT genotype and 18.33% TT genotype, while in controls, it was 18.46% and 1.54%, respectively. The TT genotype increased the risk of NSCLP (odds ratio [OR] =0.079, 95% confidence interval [CI]: 0.02–0.34, P = 0.0007) and CT genotype decreased the risk (OR = 2.59, 95% CI: 1.11–6.06, P = 0.028). However, CT + TT model had no association with NSCLP when compared to CC genotype. No significant difference was found between other 59 clefts and polymorphism. Discussion and Conclusion: The association of MTHFR C677T polymorphism with NSCLP varies from population to population. Our study found an association between the polymorphism and NSCLP. The TT genotype increased the risk of NSCLP and CT genotype reduced the risk.

Association of MTHFR C677T polymorphism with weight gain induced by risperidone in schizophrenia

Objective To explore the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with weight gain induced by risperidone. Methods 356 patients with schizophrenia according to the DSM-IV criteria in this study. The height and body weight of the patients were measured before starting risperidone treatment and 8-week later. The MTHFRC677T polymorphism was genotyped using direct DNA sequencing method. Results A significant association was found between MTHFR gene C677T and body weight mass index (BMI) change after 8-week risperidone treatment. CC-carriers experienced higher BMI gain than CT/TT-carriers (CC(4.47±1.09), CT(4.54±1.27), TT(2.31±0.75), F=5.634, P 7%) was higher than that in non-bodyweight gain groups (48.4% vs 32.4%, χ2=11.342, P<0.01). Conclusion MTHFRC677T polymorphism is associated with risperidone induced weight gain in Chinese Han population. Key words: Schizophrenia; MTHFR gene; Antipsychotics; Body weight gain

Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P).

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigentic process of DNA methylation. It has been reported that abnormal DNA methylation contributes to the pathogenesis of congenital anomalies. There were many published case control studies assessing the associations of MTHFR C677T polymorphism with risks of nosyndromic cleft lip with and without palate (nsCL/P), but with inconsistent results. To derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified by search of databases including PubMed, Science Direct, Google Scholar and Springer Link up to December, 2015. Finally, a total of 22 studies with 3724 nsCL/P cases and 5275 controls were included in the present meta-analysis. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association. Subgroup analysis based on ethnicity was also performed. All statistical analyses were done by MIX program. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased nsCL/P risk in overall population using four genetic models except homozygote model (for T vs. C: OR=1.24, 95% CI=1.1-1.4; for TT+CT vs. CC: OR=1.29, 95% CI=1.04-1.59; for CT vs. CC: OR=1.26, 95% CI=0.98-1.63; for TT vs. CC: OR=1.02, 95% CI=0.74-1.4; for TT vs. CT+CC: OR=1.36, 95% CI=1.05-1.74). In conclusion, results of present meta-analysis suggested that MTHFR C677T polymorphism is significantly associated with nonsyndromic orofacial cleft.

Associations of MTHFR C677T polymorphism with insulin resistance, results of NURSE Study (Nursing Unacquainted Related Stress Etiologies)

BackgroundThe insulin resistance syndrome is one of the major contributors of metabolic syndrome, diabetes Type 2 and atherosclerotic cardiovascular disease. A common mutation (677C to T; Ala to Val) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased specific MTHFR activity and elevation of the homocysteine. The aim of this study is investigation of association between MTHFR 677C > T polymorphism with insulin resistance by using HOMA (Homeostasis Model Assessment) index in nurses who are potentially prone to develop insulin resistance because of unfavorable effects of shift work.MethodNursing Unacquainted Related Stress Etiologies Study (Nurse Study) was conducted in five different educational hospitals of Tehran University of Medical Science (TUMS). The nurses aged 22–57 who have been referred by the matron were recruited. A self-administered questionnaire was completed. Anthropometric measurements including weight, height, waist and hip circumference in addition to blood pressure were measured. Insulin resistance and Insulin sensitivity were measured using the homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) respectively. The detection of MTHFR C677T polymorphism in exon four of MTHFR gene was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis using HINFI restriction enzyme digestion.ResultA total of 273 subjects were recruited in the study. CT genotype were detected in 51.6% (129) subjects and CC and TT genotype were seen in 9.2% (25) and 35.2% (96) subjects respectively. Participants with TT genotype (9.65 ± 4.00) have significantly lower insulin level than participants with CT genotype (14.12 ± 15.34) (p-value: 0.01). The same significant difference was observed for HOMA index (p-value: 0.03). Result showed that HOMA is lower in subjects who are taking supplements.ConclusionResult of this study showed subjects with TT genotype had significantly lower HOMA compare to CT genotype and the same pattern was seen for insulin level. We also found subjects taking supplement have lower HOMA compared to others regardless of their genotype.

MTHFR C677T polymorphism and breast, ovarian cancer risk: a meta-analysis of 19,260 patients and 26,364 controls.

ObjectivePrevious studies have found that many gene variations can be detected in both breast cancer and ovarian cancer, which is beneficial for the elaboration of the molecular origin of breast and ovarian cancer. Furthermore, many studies have explored the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with the risk of breast cancer and/or ovarian cancer; however, the results remained inconclusive. Therefore, this study conducted a systematic review and meta-analysis to evaluate the association between MTHFR C677T polymorphism and the risk of breast and ovarian cancer.Materials and methodsA total of 50 studies with 19,260 cases and 26,364 controls including 39 studies for breast cancer and 8 studies for ovarian cancer were identified on searching through PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP). Allele model, dominant model, recessive model, homozygous model, and co-dominant model were applied to evaluate the association of MTHFR C677T polymorphism with breast cancer and/or ovarian cancer risk. Moreover, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between MTHFR C677T polymorphism and breast and ovarian cancer risk.ResultsA significantly increased breast cancer risk was observed in the overall analysis (for C vs T, OR =1.19, CI: 1.12–1.28, P<0.05; for CC vs TT, OR =1.20, CI: 1.10–1.23, P<0.05; for (CT+CC) vs TT, OR =1.19, CI: 1.11–1.27, P<0.05; for CC vs (CT+TT), OR =1.19, CI: 1.79–1.95, P<0.05), while no significantly increased ovarian cancer risk was detected. In the subgroup analysis based on ethnicity, a significant association of breast cancer and/or ovarian cancer risk with MTHFR C677T polymorphism was observed in Asians. Interestingly, there was no significant association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians, whereas a significantly increased risk of breast cancer was found in Caucasians.ConclusionThis meta-analysis demonstrates that MTHFR C677T polymorphism may be a risk factor for breast and ovarian cancer, especially in Asians.

Association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with preterm delivery and placental abruption: a systematic review and meta-analysis.

The aim of this study was to summarize evidence on the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and odds of preterm delivery and placental abruption. PubMed, EMBASE, CBM (Chinese Biomedical Database) and CNKI (Chinese National Knowledge Infrastructure) were searched to identify eligible studies published in English or Chinese before 12 August 2014. The pooled odds ratios (ORs) with 95% confidence intervals were estimated for the association of MTHFR C677T polymorphism with preterm delivery and placental abruption using random effects models. A total of 22 studies that met inclusion and exclusion criteria were included in this meta-analysis. Regardless of the genetic model tested we found no statistically significant association of MTHFR C677T polymorphism with preterm delivery or placental abruption. Funnel plots inspections, Begg's test and Egger's test did not show evidence of publication bias. This meta-analysis demonstrated that overall there was no association of MTHFR C677T polymorphism with preterm delivery or placental abruption.

Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to Alzheimers disease (AD) was controversial in previous studies. The present meta-analysis was designed to investigate the association of MTHFR C677T polymorphism with AD. Nine studies were identified by search of PubMed, Google Scholar, Elsevier, Springer Link databases, up to January 2013. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated using fixed effects model or random effects model. All statistical analysis was done by Mix version 1.7. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C: OR 1.29, 95% CI 1.15-1.44, p<0.0001; for TT+CT vs CC: OR 1.38, 95% CI 1.16-1.364, p=0.0002; for TT vs CC: OR 1.60, 95% CI 1.25-2.04, p=0.0001; for CT vs CC: OR 1.28, 95% CI 1.1-1.53, p<0.008; for TT vs CT+CC: OR 1.37, 95% CI 1.12-1.67, p=0.002). Results from present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD in Asian population.

Association between MTHFR C677T polymorphism and venous thromboembolism risk in the Chinese population: a meta-analysis of 24 case-controlled studies.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and venous thromboembolism (VTE) risk in the Chinese population has been widely reported, but results were inconsistent and underpowered. To elucidate the variable results, a meta-analysis and systematic review were performed from all case-controlled studies relating MTHFR C677T polymorphism by pooling data on them. We estimated the pooled odds ratio with its 95% confidence intervals to assess this possible association. Finally, a total of 24 studies with 2339 cases and 4048 controls were included in the current meta-analysis. Significant association was found with VTE risk for all genetic models. Subgroup analyses by type of VTE further identified the above-mentioned association in deep vein thrombosis/pulmonary embolism and splanchnic vein thrombosis. The findings from our meta-analysis support the associations of MTHFR C677T polymorphism with VTE risk in the Chinese population.

Significant Association Between MTHFR C677T Polymorphism and Thyroid Cancer Risk: Evidence from a Meta-Analysis

Many studies were published to assess the associations of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with thyroid diseases, including thyroid cancer, but the results were controversial. A comprehensive search was performed in the Pubmed, Embase, and Chinese Biomedical Database (CBM) databases or published studies investigating the associations of MTHFR C677T polymorphism with thyroid diseases. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to assess the possible associations. Nine studies with a total of 2421 individuals were finally included into the meta-analysis. Meta-analysis of nine studies showed that there was no association between MTHFR C677T polymorphism and thyroid diseases (OR (T vs. C) =1.09, 95% CI 0.94-1.26, p=0.25; OR (TT vs. CC) =1.04, 95% CI 0.75-1.42, p=0.83; OR (TT vs. CC/CT) =1.13, 95% CI 0.86-1.50, p=0.37; OR (TT/CT vs. CC) =1.22, 95% CI 0.88-1.68, p=0.24). Meta-analysis of studies on thyroid cancer showed that there was an obvious association between MTHFR C677T polymorphism and increased risk of thyroid cancer in Caucasians (OR (T vs. C) =1.30, 95% CI 1.03-1.65, p=0.03; OR (TT vs. CC) =2.06, 95% CI 1.04-4.10, p=0.04; OR (TT vs. CC/CT) =2.02, 95% CI 1.02-3.92, p=0.04). There was no obvious risk of publication bias in the meta-analysis. This meta-analysis suggests that there is a significant association between MTHFR C677T polymorphism and thyroid cancer risk in Caucasians.

Association of MTHFR C677T polymorphism and risk of cerebrovascular disease in Chinese population: an updated meta-analysis

A variety of epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and cerebrovascular disease, but the results were inconsistent. The present meta-analysis was therefore performed to investigate the relationship between C677T polymorphism and cerebrovascular disease in Chinese population. Systematically searching for related studies from PubMed, Embase, Web of Science, CBMdisc and CNKI databases up to 20 September 2013 and manual searching of the reference lists of identified articles was performed. Information was extracted to calculate for the additive, dominant, and recessive models using the pooled odds ratios (ORs) along with 95 % confidence intervals (CIs), using Review Manager 5.0, STATA 11.0 and SPSS 17. Logistic regression, fixed or random effects model, subgroup analysis, sensitivity analysis, meta-regression analysis and publication bias were conducted to improve the comprehensive analysis. A total of 68 case-control studies containing 7,990 cases and 6,941 controls were included in the final meta-analysis. Evidence of significant association between C677T polymorphism and risk of cerebrovascular disease was found in all three genetic models (additive model OR 1.472, 95 % CI 1.368-1.585, P L < 0.001 (CT vs. CC); OR 1.819, 95 % CI 1.666-1.985, P L < 0.001 (TT vs. CC); dominant model OR 1.77, 95 % CI 1.57-1.98, p < 0.00001; and recessive model OR 1.54, 95 % CI 1.39-1.71, p < 0.00001, respectively) based on the overall population. In addition, the results were verified by the subgroup analysis and sensitivity analysis. The present meta-analysis suggests that MTHFR gene C677T polymorphism is significantly associated with increased risk of cerebrovascular disease. TT genotype may act as an independent risk factor for cerebrovascular disease in Chinese population.

Positive association between MTHFR C677T polymorphism and oral cancer risk: a meta-analysis

Methylenetetrahydrofolate reductase (MTHFR) is a central enzyme involved in regulating the metabolic function of folate, which plays a pivotal role in DNA synthesis, repair, and methylation. The role of MTHFR C677T polymorphism in oral cancer risk has been reported with conflicting evidence. We conducted this study to appropriately estimate the effect size. We searched eligible studies in medicine-specific databases (PubMed, EMBASE, and Web of Knowledge) using (polymorphism) OR (polymorphisms) AND (methylenetetrahydrofolate reductase) OR (MTHFR) AND (oral cancer). A total of seven studies were summarized. This meta-analysis of the combined data showed a marginal association of MTHFR C677T polymorphism with oral cancer risk [odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.73-1.00 for CT vs. CC]. We also found decreased oral cancer risk in Asian population and hospital-based studies. Moreover, heavy drinkers were found to have a significantly higher risk of developing such cancer as compared to the non-heavy drinkers. These results suggest that MTHFR C677T polymorphism may play a role in oral cancer carcinogenesis in Asian population and heavy drinkers.

MTHFR gene polymorphism and age of onset of schizophrenia and bipolar disorder.

Objective. Several studies with contradictory results from different cultures about association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in schizophrenia and bipolar disorders. Little is known about this association in Arab culture and Egypt. So the present study aimed to assess the association of MTHFR C677T polymorphism in bipolar disorder (BD) and schizophrenia in comparison to control group. The association between MTHFR C677T polymorphism and the age at onset in schizophrenia or BD was also studied. Methods. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the genotype and allele frequencies of MTHFR C677T polymorphism in 149 healthy subjects and 134 bipolar and 103 schizophrenia patients. Results. In BD and schizophrenia, there was a higher prevalence of MTHFR C677T polymorphism than healthy subjects. Earlier age at onset was found in patients with BD, carrying one copy of the T allele or CT genotypes but not in patients with schizophrenia. Conclusion. The present findings suggest that the MTHFR C677T polymorphisms are likely to be associated with the risk of developing BD and schizophrenia and influence the age at onset of BD but not the age at onset of schizophrenia.

Diet Folate, DNA Methylation and Polymorphisms in Methylenetetrahydrofolate Reductase in Association with the Susceptibility to Gastric Cancer

Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with DNA methylation, an epigenetic feature frequently found in gastric cancer. We conducted a case-control study to explore the association of MTHFR C677T polymorphisms with gastric cancer risk and its relation with the DNA methylation of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined by methylation-specific PCR after sodium bisulfate modification of DNA, and genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. Folate intake was calculated with the aid of a questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors. Individuals who had an intake of folate above 310 μg/day showed protective effects against gastric cancer risk. The effect of MTHFR C677T polymorphisms on the risk of gastric cancer was modified by folate intake and methylation status of MGMT (P for interaction <0.05).

Association of MTHFR C677T polymorphism with schizophrenia and its effect on episodic memory and gray matter density in patients

Growing evidence suggests that the methylenetetrahydrofolate reductase (MTHFR) may play a role in the pathogenesis of schizophrenia. Recent studies suggested that the MTHFR 677T, as a risk allele, has an impact on brain activation and memory function in schizophrenia patients. To confirm further the association between this functional polymorphism and schizophrenia, we detected genotypes of MTHFR C677T polymorphism in 1002 schizophrenic patients and 1036 controls of Chinese Han population, by using direct DNA sequencing method. To explore further effects of MTHFR C677T polymorphism on memory and brain function in schizophrenia, 33 schizophrenia patients and 29 healthy participants were selected from above samples to be assessed with MRI scanning and episodic memory (EM) examination. The case-control association study results showed that the MTHFR C677T was associated with schizophrenia (χ2=14.11, P=1.74×10−4, OR=0.79; 95% CI=0.70–0.89). We also found that the MTHFR 677T allele had a load-dependent effect on EM in schizophrenic patients, but not in healthy control participants. Further analysis on gray matter density (GMD) revealed significant diagnostic effects in bilateral frontal cortices, bilateral insula, left medial temporal cortex and bilateral occipital cortices, effects of MTHFR genotype in the right insula, right inferior frontal gyrus, right rolandic opercula, right parahippocampal gyrus and right medial temporal pole, and effects of genotype-diagnosis interaction in the right temporal gyrus. Our findings suggested that the MTHFR 677T allele might have effect on risk of schizophrenia, memory impairment and GMD changes in patients.

Association of MTHFR C677T polymorphism with loneliness but not depression in cognitively normal elderly males

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is involved in folate and homocysteine metabolism, and has been associated with geriatric disorders, including dementia and late-life depression. The present work aimed to investigate the effect of MTHFR C677T polymorphism on the presence of depression and loneliness in cognitively normal male subjects. A total of 323 cognitively normal male subjects were included in this study (mean age=80.6; SD=5.3). Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Analysis of variance (ANOVA) was used to test the between MTHFR genotype difference in depression and loneliness. Multiple regression was used to test the effect of MTHFR polymorphism on the loneliness, controlling for age, education, cognitive function, and depression. ANOVA showed a significant between-genotype difference in loneliness scores (P=0.015), and post hoc comparisons showed that subjects with C/C genotype had significantly higher loneliness ratings, compared to those with C/T or T/T genotype. Regression analysis indicated that the effect of MTHFR polymorphism on loneliness was independent of age, education, cognitive function, and depression. Our findings suggest that MTHFR C677T polymorphism may be linked more to loneliness than depression in the cognitively normal elderly males, and may be implicated in the pathophysiology of late-life depression in relation to MTHFR genes.