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.

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.

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.

Biochemical association between the prevalence of genetic polymorphism and myocardial infarction

Genetic polymorphism has a vital role in the pathogenesis and development of myocardial infarction(MI).Single nucleotide polymorphism at any one of the amino acid sequences can result in a diseased state.A single gene can exhibit genetic polymorphism at more than one position giving rise to different variants.Genetic polymorphism of angiotensinogen(AGT)M235T,AGT T174M,and angiotensin-1-converting enzyme(ACE)I/D,endothelial nitric oxide synthase(eNOS),and methylenetetrahydrofolate reductase(MTHFR)can be a risk factor for MI.However,it is important to study the prevalence of genetic polymorphisms of these genes among different populations.MI is influenced by genetic polymorphism of various genes,including AGT,ACE,eNOS,MTHFR,etc.However,the association of genetic polymorphism of these genes varies among different populations,but different ethnic groups could show contradictory results.These genes have shown a positive association with risks of MI in some populations,whereas the results have not been consistent with every ethnic group.In this article,we have summarized the genetic variations in the aforementioned genes and their association with MI.

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.

MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2 gene in transitional cell carcinoma of the bladder

The purpose of this study was to determine the relationship between methylation status of the insulin-like growth factor 2 （IGF-2） gene and methylenetetrahydrofolate reductase （MTHFR） C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism （RFLP）, PCR-based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF-2 gene. The association between the methylation status of the IGF-2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all normal bladder tissues. The hypomethylation rate of the IGF-2 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis （46.3% vs 17.2%, P = 0.018）. No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the variant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF-2 gene. Compared with wildtype CC, the odds ratio was 4.33 （95% CI=1.06-10.59） for CT and 4,95 （95% CI=1.18-12.74） for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.

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.

Association between MTHFR A1298C Polymorphism and Male Infertility：A Meta-analysis

There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase（MTHFR） A1298 C polymorphism and the risk of male infertility.However,the results obtained were inconsistent.Therefore,we performed a meta-analysis to further examine the association between the MTHFR A1298 C polymorphism and male infertility.A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15 th,2016.A total of 20 studies with 4293 cases and 4507 controls were included.An odds ratio（OR） and a 95% confidence interval（95% CI） were calculated to assess the strength of the association.A cumulative meta-analysis,sensitivity analysis and assessment of the publication bias were also performed in this study.The results showed that in the overall analysis,the association between the MTHFR A1298 C polymorphism and male infertility was not significant.A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298 C polymorphism（especially in the heterozygote model：OR=1.20,95% CI=1.01–1.44,P=0.994;the dominant model：OR=1.23,95% CI=1.04–1.45,P=0.996;and the allele model：OR=1.20,95% CI=1.04–1.39,P=0.985） but not in the Caucasian population.In the stratified analyses,no significant association was observed between the different types of male infertility.This meta-analysis suggests the MTHFR A1298 C polymorphism may be a potential risk factor for male infertility,especially in the Asian population.

May headache be the first sign of mutation in the MTHFR gene?

BACKGROUND:Cerebral venous thrombosis(CVT) is a rare disease and it has different etiologies.Inherited or acquired prothrombotic state plays a key role in the development of CVT.METHODS:A 28-year-old man who presented to our emergency department with persistent headache and accompanied by complaints of nausea and vomiting over a week.Neurologic examination revealed bilateral papilledema.Brain computed tomography showed a hyperdense area on the posterior part of the occipital lobe.Brain magnetic resonance imaging and magnetic resonance venography revealed thrombosis of CVT.Homozygous mutations were found for methylenetetrahydrofolate reductase(MTHFR).MTHFR CG677 T gene mutation and blood tests showed elevated homocysteine levels on the etiological screening.There was no other etiology for CVT.RESULTS:Headache and other complaints were improved after treatment of heparin,warfarin,and vitamin B12.No recurrence of symptoms was observed upon outpatient follow-up.CONCLUSION:Since CVT is an important cause of headache,we recommend etiology screening for patients who present with CVT for MTHFR gene mutations and family counseling should be provided.

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.

Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women:a meta-analysis

Osteoporosis is a condition characterized by low bone mineral density （BMD） and micro-architectural changes in the bone tissue.The risk of osteoporosis is partly determined by genetic factors.The role of C677T polymorphism of methylenetetrahydrofolate reductase （MTHFR） gene has been investigated in postmenopausal osteoporosis.However,the relationship between MTHFR polymorphism and BMD is still controversial.We carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal women.Databases of MEDLINE,Web of Science,Scopus and CNKI were retrieved for all publications relating to MTHFR polymorphism and BMD in postmenopausal women.Five eligible studies were selected for meta-analysis.All these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal women.Our analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype,and the weighted mean difference （WMD） was-0.01 g/cm 2 [95% confidence interval （CI）：（-0.01,-0.01）,P 0.01].However,BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT genotype.In the random effects model,the WMD between the TT and TC/CC genotype was-0.01 g/cm 2 [95% CI：（-0.04,0.01）,P=0.32].The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal women.Women with the TT genotype of the MTHFR gene have lower BMD,suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.

Study of A1298C MTHFR Gene Polymorphism as a Risk Factor for Neural Tube Defects in the Eastern Algerian Population

Background: As C677T mutation, A1298C mutation in methylene tetrahydrofolate reductase (MTHFR) gene results in a decreased MTHFR activity but to a less extent, it is known as a risk factor of predisposition to human neural tube defects (NTDs), in some populations. Our objective was therefore to study, for the first time in Algerian population, if A1298C polymorphism confers risk for the occurrence of this abnormality. We have examined the distribution of the genotype and the allele frequencies of A1298C mutation, and also their influence on plasma homocysteine (Hcy) concentration. Patients and Methods: We studied this polymorphism in 38 mothers of NTD cases and 67 control individuals of an eastern Algerian population. The mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR/RFLP). Plasma homocysteine concentration was analyzed using an automated chemiluminescence method. Results: No signi?cant association could be observed between allele and genotypes frequencies of A1298C MTHFR gene polymorphism and NTDs risk. However, we could observe that A1298C polymorphism affects homocysteine metabolism in mothers of NTD cases leading to homocysteine concentration values higher in AA genotype and lower in AC/CC genotypes (15.29 ± 11.8 μmol/l vs. 8.63 ± 3.83 μmol/l, p < 0.05). Conclusion: Data indicate that A1298C MTHFR gene polymorphism might be a risk factor by affecting homocysteine metabolism in mothers of Algerian children with NTDs.

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic

Genetic risk factors have been shown to contribute to the development of sexual dysfunction.However,the role of methylenetetrahydrofolate reductase(MTHFR)gene variants in the risk of erectile dysfunction(ED)remains unclear.In this study,we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5.The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction(PCR).No significant difference in the genotypic frequency of the MTHFR C677T polymorphism(CC,CT,and TT)was observed between men from the ED and non-ED groups.In addition,on binary logistic regression analysis,both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism.Interestingly,a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED(P=O.02).The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis,even after adjusting for potential confounders(odds ratio[OR]=2.46,95%confidence interval[CI]:1.15-5.50,P=0.02).These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED.Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routineclinicaldiagnosis.

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.

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.

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip/palate in northern Venezuela

Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.

The relationship between MTHFR gene polymorphisms, plasma homocysteine levels and diabetic retinopathy in type 2 diabetes mellitus

Objective To evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in patients with type 2 diabetes mellitus and diabetic retinopathy (DR). Methods Total of 208 patients with type 2 diabetes mellitus and 57 controls were recruited into the study. MTHFR genetic C677T polymorphisms were determined by PCR-RFLP. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. Results The frequencies of MTHFR TT homogeneous type, CT heterogeneous type and allele T (28.18%, 41.82%, 49.09%) were significantly higher in the type 2 diabetes mellitus with diabetic retinopathy group than those without retinopathy (18.37%, 29.59%, 33.16%) and those of controls (17.54%, 28.07%, 31.58%). The presence of the T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 with a 95% confidence interval of 1.31-2.88. Moreover, plasma homocysteine levels were remarkably higher in patients with TT or CT genotype than in patients with the CC genotype. Conclusion MTHFR gene C677T mutation associated with a predisposition to increased plasma homocysteine levels may be considered as a genetic risk factor for diabetic microangiopathy (such as DR) in Chinese patients with type 2 diabetes mellitus.