Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia

Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.

Interaction of methylenetetrahydrofolate reductase C677T,cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population

AIM： To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase （MTHER） and cytochrome P4502E1 （CY- P4502E1）, environment risk factors with esophageal cancer （EC） in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China. METHODS： A 1：2 matched case-control study was conducted with 120 cases of EC and 240 populationor hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism （RFLP）. A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis. RESULTS： Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water （shallow well, or river） were found to be the risk factors for EC. Individuals with the MTHFR677 （C/T ＋ T/T） genotype had a 2.62-fold （95% CI： 1.61-4.28） risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502EIC1/C1 genotype had a 3.00-fold （95% CI： 1.82-4.96） risk compared with those who carried the CYP4502E1 （C1/C2 ＋ C2/C2） genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 （C/T ＋ T/T） and CYP4502EIC1/ C1 genotypes had a 7.41-fold （95% CI： 3.60-15.25） risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 ＋ C2/C2 genes, and the interaction rate was higher than that of the two factors alone. CONCLUSION： Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water （shallow well, or river） and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.

Serum Folate, MTHFR C677T Polymorphism and Esophageal Squamous Cell Carcinoma Risk

This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions （EPL） and esophageal squamous cell carcinoma （ESCC）. The highest quartile of serum folate concentration significantly decreased the risk of ESCC compared with the lowest quartile （0R=0.11; 95% CI, 0.04-0.33; P〈0.05）. MTHFR 677 C〉T polymorphism was associated with the risk of ESCC by using chi-square tests （P〈0.05）. For the CT genotype, the risk of ESCC significantly increased in study participants with low serum folate concentrations （〈26.92μg/L） compared with participants with high serum folate concentrations （〉26.92 μg/L） by using multinomial logistic regression models. The MTHFR genotype may further modify associations between serum folate concentrations and the risk of ESCC, but it was not significantly associated with the risk of EPL.

Methylenetrahydrofolate Reductase Gene C677T Polymorphism and Diabetic Retinopathy: a Meta-Analysis

Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T(MTHFR C677T)polymorphism and diabetic retinopathy(DR).Methods A total of 6971 subjects including 2707 DR patients and 4264 controls from 23 studies were enrolled in the study.A random-effects model was applied to estimate the overall effects and the stratified effects of the MTHFR C677T polymorphism on the risk of DR,and study quality was also assessed.Results Strong associations were observed between the MTHFR C677T polymorphism and DR.The carries of MTHFR C677T were more likely to be found in the DR group in relative to the healthy control group with odds ratio 1.6&2.55,and 2.31 respectively in allele contrast model(T vs.C,95%CZ:1.29-2.18,P<0.001,f=7&4%),homozygous model(TT vs.CC,95%CZ:1.70-3.83,P=0.008,72=54.4%)and dominant model(TT+CT vs.CC,95%CZ:1.62-3.29,P<0.001,12=74.7%).This association can also be found in contrast to the Ned(non-complicated diabetic mellitus)group(allele contrast,OR—1.50,95%Ch 1.07-2.11,P=0.032,I2=62.1%;homozygous,OR—2.39,9S%CZ:1.06-5.38,P=0.017,Z2=66.7%;dominant,OR=1.59,95%CZ:0.97-2.62,P=0.056,I2=56.5%).For the heterozygous model(CT vs.CC),the association was significant in contrast to the healthy control group(OR=1.46,95%CZ:1.64-3.69,P=0,P=77.3%),while in contrast to the Ned control group the association was not statistically meaningful(OR=1.38,95%CZ:0.87-2.18,P=0.131,Z2=43.7%).For the recessive model,1.92-fold increased risk was found only in contrast to the Ned control group(95%C1:1.07-3.43,P=0.064,P=55.0%).There was no significant association found in the models in contrast to the DM control group.Conclusion In this meta-analysis,we found an association between the MTHFR C677T polymorphism and DR,especially in contrast to the Ned control group.Further studies are required to establish more definite relationship.

Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma

AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its most common genetic determinant defect, the methylenetetrahydrofolate reductase C677T (C677TMTHFR) polymorphism in patients with early stage colorectal carcinoma. METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for C677TMTHFR substitution was performed by PCR and restriction analysis. RESULTS: The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism did not differ between the groups. The mean tHcy was statistically higher in cancer patients than in control subjects carrying the same C/C or C/T genotype, whereas there was no difference in the T/T homozygous carriers of the two groups. tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T genotype carriers. CONCLUSION: The statistically significant increase of tHcy observed in C/C and C/T genotype carriers among our cancer patients is related to substrate consumption dependent on the tumor cell proliferation rate, whereas the tHcy increase observed in T/T genotype carriers of both groups probably depends on the enzymatic deficit of the homocysteine conversion to methionine and/or on the folate deficiency.

Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

Objectives The association of methylenetetrahy-drofolate reductase(MTHFR) gene polymorphism and serum lipid profiles is still controversial in diverse ethnics.Bai Ku Yao is an isolated subgroup of the Yao minority in China. The aim of the present study was to eveluate the association of MTHFR C677Tpolymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Methods A total of 780 subjects of Bai Ku Yao and 686 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples.Genotyping of the MTHFR C677T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing.Results The levels of serum total cholesterol(TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol(LDL-C), apolipoprotein(Apo) AI and ApoB were lower in Bai Ku Yao than in Han(P【0.05-0.001).The frequency of C and T alleles was 77.4%and 22.6%in Bai Ku Yao,and 60.9%and 39.1%in Han(P【0.001);respectively.The frequency of CC,CT and TT genotypes was 58.7%,37.3%and 4.0%in Bai Ku Yao,and 32.6%,56.4%and 11.0%in Han(P【 0.001);respectively.The levels of TC and LDL-C in both ethnic groups were significant differences among the three genotypes(P【0.05-0.01).The T allele carriers had higher serum TC and LDL-C levels than the T allele noncarriers. The levels of ApoB in Han were significant differences among the three genotypes(P【0.05).The T allele carriers had higher serum ApoB levels as compared with the T allele noncarriers. The levels of TC,TG and LDL-C in Bai Ku Yao were correlated with genotypes(P【0.05-0.001),whereas the levels of LDL-C in Han were associated with genotypes(P【 0.001).Serum lipid parameters were also correlated with sex, age,body massindex,alcohol consumption,cigarette smoking, and blood pressure in the both ethnic groups.Conclusions The differences in serum TC,TG,LDL-C and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of the MTHFR C677Tor differentMTHFR gene-enviromental interactions.

Relationship between granulomatous lobular mastitis and methylene tetrahydrofolate reductase gene polymorphism

BACKGROUND Variations in the methylene tetrahydrofolate reductase(MTHFR)gene have been reported as risk factors for numerous conditions,including cardiovascular disease,thrombophilia,stroke,hypertension and pregnancy-related complications.Moreover,it was reported there is an association between breast cancer and mutations in MTHFR-C677T.However,whether there is an association between MTHFR gene polymorphism and granulomatous lobular mastitis or not has been rarely investigated.AIM To analyze the association between MTHFR gene polymorphism and granulomatous lobular mastitis.METHODS Fifty-one patients with granulomatous lobular mastitis admitted to The First Hospital of Kunming were selected as study samples.Their hospitalization time ranged from February 2018 to February 2019.The 51 patients were included in the experimental group,and another 51 women who underwent physical examination at The First Hospital of Kunming in the same period were included in the control group.Deoxyribonucleic acid and MTFR genetic polymorphism testing were performed in each group.The association between MTHFR gene polymorphism and granulomatous lobular mastitis was observed.RESULTS There were significant differences in genotype frequency and allele frequency of C/C and C/T between the experimental group and the control group(all P<0.05).However,there was no significant difference in frequency of T/T genotype between the two groups(P>0.05).In addition,there was no significant difference in genotype frequency and allele frequency of A/A,A/C and C/C between the two groups(P>0.05).CONCLUSION MTHFR gene C677T locus polymorphism is closely related to granulomatous lobular mastitis.

Stroke Due to Hypercoagulable State Can Mimic Multiple Sclerosis: A Case Report

Introduction: Stroke is the second major cause of mortality worldwide and in several cases, and it may lead to disability. Factor V Leiden is a common genetic thrombophilia, which causes activated protein C (APC) resistance. Hyperhomocysteinemia and factor V Leiden deficiency, two independent coagulopathy factors, can lead to venous and arterial infarctions in multiple small and large arteries and veins anywhere in the body. Case Report: Here, we report a unique case in which both hyperhomocysteinemia and factor V Leiden deficiency are documented together with MTHFR (C677T) (Methylene Tetra Hydro Folate Reductase) gene polymorphism and activated protein C resistance respectively. Conclusion: More interestingly, the mode of presentation in this case highly resembled that of progressive multiple sclerosis;all signs and symptoms slowly progressed without any systemic signs at first few years. Further studies needed to assess current outcomes.

The combination of methylenehydrofolate reductase C677T polymorphism screening and gastrointestinal tumor markers detection may be an early screening method for gastrointestinal cancer related to helicobacter pylori infection

Methyltetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism,and its single nucleotide polymorphism(SNP)site C677T may be associated with gastrointestinal cancer.However,the relationship between MTHFR C677T polymorphism and gastrointestinal tumor markers carcinoma embryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)in Helicobacter pylori(H.pylori)infection is not specified.This study aims to identify the association between MTHFR C677T polymorphism and gastrointestinal tumor markers(CEA,CA199 and CA724)in H.pylori infection.The relationship between MTHFR C677T polymorphism and gastrointestinal tumor markers in 58 patients with H.pylori infection and 94 non-infected patients was studied.We found that TT genotype was a susceptibility factor of H.pylori infection,which was also associated with increased CEA and CA724 levels.Moreover,there was a negative additive interaction between MTHFR gene C677T polymorphism and CEA levels in H.pylori infection.Meanwhile,there were significant differences in CEA levels between MTHFR C677T polymorphism and H.pylori infection.The presence of T allele led to a decrease in CEA levels when ^(13)C urea breath test(^(13)C-UBT)was positive,while the presence of T allele led to an increase in CEA levels when ^(13)C-UBT was negative.Therefore,we suggest that healthy people should take MTHFR C677T polymorphism screening,combined with ^(13)C-UBT and gastrointestinal tumor markers detection,which can screen out the susceptible population of H.pylori,and help to detect gastrointestinal cancer in the early stage.

Effect of enalapril on plasma homocysteine levels in patients with essential hypertension

Objective:To investigate the effect of enalapril on plasma homocysteine(Hcy) levels and the association of methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism with the changes of Hcy levels in response to enalapril among patients with essential hypertension.Methods:A total of 130 patients with mild-to-moderate essential hypertension were enrolled and enalapril was orally administered at a dose of 10 mg/d for eight weeks.Plasma Hcy levels were measured by denaturing high-performance liquid chromatography(DHPLC) at baseline and after eight weeks of treatment.Genotyping of MTHFR C677T polymorphism was performed by TaqMan probe technique.Results:Compared with baseline,plasma Hcy levels did not change significantly after eight weeks(P=0.81).Stratified by baseline Hcy levels,a significant increase in plasma Hcy levels(P=0.02) among those with Hcy <10 μmol/L was observed,in contrast to no significant changes in plasma Hcy levels(P=0.54) among those with Hcy ≥10 μmol/L.No significant association was observed between MTHFR C677T polymorphism and changes in Hcy levels in response to enalapril.Conclusions:Enalapril may cause an increase in plasma Hcy levels among the hypertensives with low baseline Hcy levels.There was no significant association between MTHFR C677T genotypes and changes in Hcy levels in response to enalapril among subjects with essential hypertension.