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.

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia

Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Relationship Between Polymorphism of Methylenetetrahydrofolate Dehydrogenase and Congenital Heart Defect

To investigate the relationship between G1958A gene polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital heart disease (CHD) in North China. Methods One hundred and ninety-two CHD patients and their parents were included in this study as case group in Liaoning Province by birth defect registration cards, and 124 healthy subjects (age and gender matched) and their parents were simultaneously selected from the same geographic area as control. Their gene polymorphism of MTHFD G1958A locus was examined with PCR-RFLP, and serum folic acid and homocysteine (Hcy) levels were tested with radio-immunoassay and fluorescence polarization immunoassay (FPIA). Results There existed gene polymorphism at MTHFD G1958A locus in healthy subjects living in North China. The percentages of GG, GA, and AA genotype were 57.98%, 35.57%, and 6.45% respectively, and the A allele frequency was 24.23%, which was significantly different from Western population. No difference was observed when comparing genotype distribution and allele frequency between the case and control groups, so was the result from the comparison between genders. The A allele frequency of arterial septal defect patients’ mothers (10.87%) was significantly lower than that of controls (28.15%) (P=0.014), with OR=0.31 (95% CI: 0.09-0.84), and no difference in the other subgroups. The percentage of at least one parent carrying A allele in arterial septal defect subgroup (43.48%) was significantly lower than that in controls (69.64%) (P=0.017), with OR=0.34 (95% CI: 0.12-0.92). The analysis of genetic transmission indicated that there was no transmission disequillibrium in CHD nuclear families. Their serum folic acid level was significantly higher than that of controls (P=0.000), and Hcy level of the former was higher than that of the latter with no statistical significance (P>0.05). Serum Hcy and folic acid levels of mothers with gene mutation were lower than those of mothers with no mutation. Conclusion No significant difference of genotype distribution and allele frequency existed between CHD patients and healthy population. MTHFD G1958A mutation in parents (particularly in mother) can decrease the risk of arterial septal defect in offspring. The possible mechanism of protection might be mutation, which can increase MTHFD enzyme activity, folic acid metabolism and homocysteine remethylation, and decrease Hcy level.

Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis

AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation. METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls. Folate concentrations in these tissues were detected by the FOL ACS: 180 automated chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP). RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16INK4A in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21WAF1 in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype. CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesisthrough hypomethylation and overexpression of c-myc.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility

AIM: To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydrofolate reductase gene(MTHFR)polymorphisms might influence the occurrence of coronary heart disease(CHD)in T2DM patients.The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD inT2DM patients.Methods A total of 197 subjects with T2DM were studied,of which 95 patients with CHD.The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method,and compared between patients with CHD and those without CHD.Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD(P=0.011).However,there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD.Furthermore,the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine(Hey)levels(≤15μmol/L)(P=0.006),while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hey levels(>15 μmol/L)(P=0.491).Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hey levels.

Meta-analysis of 5, 10-methylenetetrahydrofolate reductase gene polymorphism as a risk factor for ischemic cerebrovascular disease in a Chinese Han population

OBJECTIVE： To assess whether 5, 10-methylenetetrahydrofolate reductase （MTHFR） gene polymorphism （TT genotype or T allele） is a risk factor for ischemic cerebrovascular disease （ICVD）. DATA SOURCES： MEDLINE and PubMed databases from September 1997 to December 2009 were searched for case-control studies that examined MTHFR genotype in human ICVD using ＂MTHFR, gene, polymorphism, and ischemic cerebrovascular disease＂ as search key words. STUDY SELECTION： Eighteen associated studies were identified. The methods used to collect relevant information factors were similar between case and control groups, and diagnosis of ischemic cerebrovascular disease was in accordance with Trial of ORG 10172 in Acute Stroke Treatment criteria classification, with some referring to European Stroke Diagnostic Criteria. Quality of all included studies was evaluated, and meta-analysis was conducted using RevMan4.2 software （Cochrane Collaboration, http：//www.cochrane-handbook.org） following strict screening. MAIN OUTCOME MEASURES： The correlation between MTHFR gene TT genotype or T allele and ICVD was determined. RESULTS： Eighteen studies involving 4 295 patients with ICVD and 6 169 control subjects were included for this meta-analysis. There was a significant difference in MTHFR gene TT genotype or T allele frequency （x^2 = 15.737, 9.186, P 〈 0.01） between ICVD cases and controls. In addition, six Chinese Han population studies were specially reviewed by meta-analysis. Results showed no significant difference between ICVD and control groups with regard to frequency of MTHFR gene TT genotype and T allele （x^2 = 1.076, 2.434, P 〉 0.05） in the Chinese Han population. CONCLUSION： Results from the present meta-analysis suggested that the MTHFR gene TT genotype or T allele is a risk factor for ICVD. However, the TT genotype or T allele is not a risk factor for ICVD in the Chinese Han population.

Is the C677T polymorphism in methylenetetrahydrofolate reductase gene or plasma homocysteine a risk factor for diabetic peripheral neuropathy in Chinese individuals?

The present study enrolled 251 diabetic patients, including 101 with neuropathy and 150 without neuropathy. Of the 150 patients, 100 had no complications, such as retinopathy, nephropathy, or neuropathy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify methylenetetrahydrofolate reductase gene variants. Plasma homocysteine levels were also measured. Homocysteine levels and the frequency of hyperhomocysteinemia were significantly higher in patients with diabetic peripheral neuropathy compared with diabetic patients without neuropathy （P 〈 0.05）. In logistic regression analysis with neuropathy as the dependent variable, the frequency of C677T in methylenetetrahydrofolate reductase was significantly higher in patients with diabetic peripheral neuropathy compared with patients without diabetic complications. Homocysteine levels were significantly higher in patients with diabetic peripheral neuropathy carrying the 677T allele and low folic acid levels. In conclusion, hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in Chinese patients with diabetes. The C677T polymorphism in methylenetetrahydrofolate reductase and low folic acid levels may be risk factors for diabetic peripheral neuropathy in Chinese patients with diabetes.

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.

Polymorphisms in methylenetetrahydrofolate reductase gene: Their impact on liver steatosis and fibrosis of chronic hepatitis c patients

Aim & Background: The mechanism of steatosis in Hepatitis C virus infection is multifactorial;therefore, it is complex and unclear. The aim of this study was to investigate the effects of methylentetrahydrofolate reductase (MTHFR) gene polymorphisms on the course of chronic hepatitis C virus infection and the development of steatosis due to hepatitis C virus. Methods: This study included 109 patients with chronic hepatitis C virus infection. Necroinflammatory activity, degrees of fibrosis and steatosis and MTHFR gene polymorphisms were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to determine MTHFR C677T and A1298C polymorphisms. Results: Fibrosis was correlated with age (r = 0.336, p = 0.002), platelet (r = ?0.448, p < 0.0001), ALT (r = 0.241, p = 0.026), AST (r = 0.361) and GGT (r = 0.224, p = 0.039). Steatosis was only correlated with fibrosis. MTHFR C677T and A1298C polymorphisms did not have a significant effect on the degree of steatosis (p = 0.857, p = 0.202 respectively). There was a relation between MTHFR C677T and the degree of fibrosis but not A1298C (p = 0.014, p = 0.187 respectively). Conclusion: We found that MTHFR C677T polymorphism contributed to the development of fibrosis in patients with chronic hepatitis C virus infection.

A review of methylenetetrahydrofolate reductase in one-carbon metabolism and psychiatric disorders

Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme for the critical process of one-carbon circulation,which convert5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate and participate in folate and homocysteine conversion correlated to methyl group supply.The enzyme activity decline depends on the gene polymorphism.MTHFR impacts on the methylation process which is related to psychiatric diseases.Studies have shown association between MTHFR gene polymorphisms and mental disorders,some of which stratified by folate and cobalamin levels.In this review,we will summarize the testimony on the relationship between methylation and MTHFR polymorphism as well as the implication on psychiatric diseases by MTHFR mutation.

Women with Methylenetetrahydrofolate Reductase Gene Polymorphism and the Need for Proper Periconceptional Folate Supplementation

Maternal folate supplementation is critical for fetal development. Women with MTHFR （methylenetetrahydrofolate reductase） gene polymorphisms may not be getting the proper folate form to support fetal development. The objectives of this review were to： （1） undertake a comprehensive review on the association of MTHFR polymorphisms with the risk for various congenital diseases and other adverse pregnancy outcomes, （2） assess the efficacy and safety of current folic acid and other supplementations in women with the MTHFR polymorphism, and （3） provide guidance on the appropriate supplementation for women of childbearing potential with the MTHFR gene polymorphism in order to decrease these adverse pregnancy outcomes. Our assessments show that women with MTHFR gene polymorphism cannot efficiently convert folic acid to L-5-methyl-tetrahydofolate, the predominant active form of folic acid, due to reduced MTHFR enzymatic activity. L-5-methyl-tetrahydrofolate is currently commercially available under several brand names. Based on our comprehensive review and knowledge of the biochemistry of the folates, we recommend that L-5-methyltetrahydrofolate be given in combination with folic acid to women with MTHFR polymorphism that are pregnant or planning to become pregnant. Further study is needed to determine the optimal dose.

Correlation of methylenetetrahydrofolate reductase polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction

Objective:To study the correlation of methylenetetrahydrofolate reductase (MTHFR) polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction.Methods: 40 patients with recurrent cerebral infarction who were treated in Yulin Third Hospital between December 2013 and December 2016 were selected as recurrent group, 58 patients with primary cerebral infarction were selected as primary group, and 60 healthy volunteers were selected as control group. Peripheral blood MTHFR gene C677T polymorphism and serum levels of Hcy metabolism indexes and inflammatory response indicators were determined.Results: CC genotype constituent ratio of recurrent group was significantly lower than that of primary group and control group while CT genotype and TT genotype constituent ratio were significantly higher than those of primary group and control group;serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group and primary group were significantly higher than those in control group while VitB12 and FA levels were significantly lower than those in control group;serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group were significantly higher than those in primary group while VitB12 and FA levels were significantly lower than those in primary group. Serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CC genotype were significantly lower than those in patients with CT genotype and TT genotype while VitB12 and FA levels were significantly higher than those in patients with CT genotype and TT genotype;serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CT genotype were significantly lower than those in patients with TT genotype while VitB12 and FA levels were significantly higher than those in patients with TT genotype.Conclusion: MTHFR gene C677T polymorphism is closely related to the recurrence of cerebral infarction, and allele C mutation to T will affect Hcy metabolism and aggravate inflammatory response.

Correlation between methylenetetrahydrofolate reductase gene C677T polymorphism and preeclampsia in pregnant women

Objective: To study the correlation between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and preeclampsia in pregnant women. Methods: Pregnant women who were diagnosed with preeclampsia in Jianshi People's Hospital between July 2014 and March 2017 were selected as the PE group of the research, and healthy pregnant women who received antenatal care and gave birth in Jianshi People's Hospital during the same period were selected as the control group of the research. The MTHFR gene C677T polymorphism in peripheral blood, the contents of homocysteine (Hcy) metabolism indexes and the expression of apoptosis genes and invasion genes were determined. Results: The proportion of MTHFR gene C677T locus TT genotype in peripheral blood of PE group was significantly higher than that of control group while the proportion of CT and CC genotypes were significantly lower than those of control group;Hcy levels in serum and placenta as well as FasL, Caspase-8, Bax, Caspase-9 and Caspase-3 mRNA expression in placenta of PE women with TT genotype were significantly higher than those of PE women with CT genotype and CC genotype while folic acid levels in serum and placenta as well as Notch-1, N-cadherin, Vimentin, CatL and CatB mRNA expression in placenta were significantly lower than those of PE women with CT genotype and CC genotype. Conclusion: MTHFR gene C677T locus mutation can participate in the occurrence of preeclampsia by affecting the Hcy metabolism as well as the expression of apoptosis genes and invasion genes.

Are all primary omental infarcts truly idiopathic?Five case reports

BACKGROUND Idiopathic omental infarction(IOI)is challenging to diagnose due to its low incidence and vague symptoms.Its differential diagnosis also poses difficulties because it can mimic many intra-abdominal organ pathologies.Although hypercoagulability and thrombosis are among the causes of omental infarction,venous thromboembolism scanning is rarely performed as an etiological investigation.CASE SUMMARY The medical records of the 5 cases,who had the diagnosis of IOI by computed tomography,were examined.The majority of the patients were male(n=4,80%)and the mean age was 31 years(range:21-38).The patients had no previous abdominal surgery or a history of any chronic disease.The main complaint of all patients was persistent abdominal pain.Omental infarction was detected in all patients with contrast-enhanced computed tomography.Conservative treatment was initially preferred in all patients,but it failed in 1 patient(20%).After discharge,all patients were referred to the hematology department for thrombophilia screening.Only 1 patient applied for thrombophilia screening and was homozygous for methylenetetrahydrofolate reductase(A1298C mutation)and heterozygous for a factor V Leiden mutation.CONCLUSION IOI should be considered in the differential diagnosis in patients presenting with progressive and/or persistent right side abdominal pain.Investigating risk factors such as hypercoagulability in patients with IOI is also important in preventing future conditions related to venous thromboembolism.

The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing,China

The methylenetetrahydrofolate reductase(MTHFR)genotypes 677CT and 677TT are associated with elevated serum homocysteine(Hcy)levels by means of lowering the activity of MTHFR,and the increase in serum Hcy may be linked to increased susceptibility to nonalcoholic fatty liver disease(NAFLD).However,there are contradictory reports of the relationship among the MTHFR 677CT gene polymorphism,Hcy,and NAFLD.Therefore,the aim of this study was to identify potential associations and interactions of either Hcy levels or the MTHFR 677CT gene polymorphism with the susceptibility to NAFLD in a Chinese population.The association between the MTHFR 677 CT gene polymorphism and Hcy levels was determined in 243 subjects with NAFLD and 388 healthy subjects without NAFLD using polymerase chain reactionrestriction fragment length polymorphism analysis and high-performance liquid chromatography.In subjects with NAFLD,there was no statistical difference in the genotypic and allelic frequencies of the MTHFR 677 CT gene polymorphism,while serum Hcy levels were significantly higher in subjects with NAFLD.Furthermore,these results strongly suggest that the MTHFR 677CT gene polymorphism and NAFLD have a potential synergistic effect on Hcy elevation,although the MTHFR 677CT gene polymorphism was not correlated with NAFLD in a Chinese population.

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Objective： The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase （MTHFR） C677T excision repair cross-complementation group 1 （ERCC1） genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods： A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regi- mens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 Cl18T were genotyped using the TaqMan methods. Results： The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype （TT or CT） （41.2% versus 19.1%, P=0.01 ）. Median time to progression （TTP） of patients with MTHFR CC genotype was longer than that of patients with variant genotype （7.6 months versus 5.0 months, P=0.003）. No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions： Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer

Background The importance of polymorphisms in the methylenetetrahydrofolate reductase （MTHFR） gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear. The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Methods Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy. DNA samples were isolated from peripheral blood collected before treatment. The three single nucleotide polymorphisms （SNPs） （rs1801131, rs1801133, rs2274976） genotypes of the MTHFR gene were determined by matrix- assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS）. Results The average response rate for chemotherapy was 46.7%. Homozygous genotypes rs2274976G/G （X2=22.7, P 〈0.01） and rs1801131A/A （X2=14.3, P=0.008） were over-represented in responsive patients. Carriers of the rs2274976A allele genotypes （G/A and A/A） and of the rs1801131C allele genotypes （A/C and C/C）were prevalent in nonresponsive patients. In the haplotype association analysis, there was a significant difference in global haplotype distribution between the groups （X2=20.69, P=0.000 124）. Conclusions These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.

Effects of methylenetetrahydrofolate reductase single-nucleotide polymorphisms on breast,cervical,ovarian,and endometrial cancer susceptibilities

Background:Recent studies identifying methylenetetrahydrofolate reductase(MTHFR)polymorphisms associated with breast cancer(BC),ovarian cancer(OC),cervical cancer,and endometrial cancer(EC)have reported conflicting results and been underpowered.To clarify the correlation betweenMTHFR mutations and these common female malignancies,we conducted a comprehensive meta-analysis incorporating all eligible publications.Methods:Relevant reports published before January 20,2020,were retrieved from PubMed,Embase,the Cochrane Library,and the China National Knowledge Infrastructure databases.The odds ratio and 95% confidence interval summaries for theMTHFR 677C/T and 1298A/C polymorphisms in BC,OC,cervical cancer,and EC were estimated.Results:A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included.The results showed a markedly elevated risk of cancer susceptibility related toMTHFR 677C/T based on all genetic models.Similarly,we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models,except the heterozygous model.Moreover,subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models.Based on ethnicity,significant associations were observed between Asian,African,and mixed populations for 677C/T and the Asian population for 1298A/C.With regard to the sample type used for analysis,we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models.Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method,as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C,respectively.Conclusion:This meta-analysis suggests thatMTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers,with these findings potentially applicable for overall comparisons of related data.

Lemierre's syndrome with double heterozygote status in the methylenetetrahydrofolate reductase gene

Background:There are some risk factors being more vulnerable to Lemierre's syndrome such as a hypercoagulable state.Methods:We report a rare case of Lemierre's syndrome with ethmoid and maxillary sinusitis,bilateral mastoiditis,and sigmoid sinus thrombosis.Results:Genetic study revealed a double heterozygote status in the methylenetetrahydrofolate reductase gene including C677T and A1298C.Conclusion:It is suggested to screen patients with Lemierre's syndrome for a hypercoagulable state to consider anticoagulant therapy.