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.

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 C677T and A1298C polymorphisms and gastric cancer susceptibility

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

MTHFR基因多态性及血清AFP水平与胎儿神经管畸形的关系

目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血清甲胎蛋白(AFP)与胎儿神经管畸形的关系。方法选取2018年1月至2023年11月在陕西省宝鸡市妇幼保健院引产或分娩的50例胎儿神经管畸形产妇作为观察组,另选取150例胎儿健康产妇作为对照组。比较两组MTHFR基因多态性分布情况及血清AFP水平,比较观察组不同MTHFR基因多态性血清AFP水平,采用多因素Logistic回归分析胎儿神经管畸形的危险因素。结果观察组MTHFR C677T基因CT基因型+TT基因型、MTHFR A1298C基因AC基因型+CC基因型比例及血清AFP水平高于对照组,差异均有统计学意义(P<0.05)。观察组MTHFR C677T基因CT基因型+TT基因型产妇血清AFP水平高于CC基因型,MTHFR A1298C基因AC基因型+CC基因型产妇血清AFP水平高于AA基因型,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,MTHFR C677T基因CT基因型+TT基因型、MTHFR A1298C基因AC基因型+CC基因型是发生胎儿神经管畸形的危险因素(P<0.05)。结论MTHFR C677T基因、MTHFR A1298C基因多态性及血清AFP水平与胎儿神经管畸形有关,在预测胎儿神经管畸形方面有一定应用价值。

血清成纤维细胞生长因子-21、亚甲基四氢叶酸还原酶基因多态性与妊娠期亚临床甲状腺功能减退症的相关性

目的 探究血清成纤维细胞生长因子-21(FGF-21)、亚甲基四氢叶酸还原酶(MTHFR)基因多态性与妊娠期亚临床甲状腺功能减退症(SCH)的相关性。方法 选取2022年7月至2023年7月山西省临汾市人民医院收诊的妊娠期SCH患者106例为SCH组,另选取院内同期孕检的健康妊娠期女性106例为健康组。收集两组病历资料,筛查SCH的相关因素,分析血清FGF-21、MTHFR基因多态性对SCH发生的评估效能。结果 SCH组的空腹血糖、血清促甲状腺素(TSH)、FGF-21高于健康组(P<0.05);两组CC、CT、TT基因型分布频率比较,差异有统计学意义(P<0.05)。SCH组T等位基因分布频率高于健康组(P<0.05)。多因素分析结果显示,血清FGF-21(OR=3.330,95%CI:1.138~9.743)、MTHFR基因多态性(OR=4.104,95%CI:1.403~12.008)是SCH发生的影响因素(P<0.05)。血清FGF-21、MTHFR基因多态性单一及联合诊断SCH发生的受试者操作特征曲线下面积分别为0.738、0.670、0.851。结论 血清FGF-21水平升高、MTHFR基因TT基因型的妊娠期女性SCH发生风险更高,两项联合具有一定的诊断价值。

亚甲基四氢叶酸还原酶基因多态性与阿尔茨海默病的相关性临床研究

目的探讨阿尔茨海默病(AD)进程中,亚甲基四氢叶酸还原酶(MTHFR)C677T多态性与疾病的相关性,以及是否受APOE基因影响。方法共纳入74例AD患者、85例遗忘型轻度认知障碍患者(aMCI)和81例健康对照者(HC),检测3组血清同型半胱氨酸(Hcy)、叶酸和维生素B12水平,以及MTHFR C677T及APOE基因型,通过Logistic回归分析比较MTHFR C677T不同等位基因和基因型分别与aMCI和AD风险之间的关联,以及在不同APOEε4亚组中的表现。结果AD组和aMCI组的血清Hcy水平均较对照组显著升高(P<0.001,P<0.001),而aMCI组血清叶酸水平较HC组明显降低(P=0.017)。与MTHFR CC、CT基因型者相比,TT基因型者的血清叶酸水平明显降低(P=0.038),血清Hcy水平明显升高(P=0.002)。回归分析结果显示:在APOEε4非携带者亚组中,MTHFR TT基因型可能增加aMCI患病风险(OR=3.670,95%CI=1.077-12.509,P=0.038),在APOEε4携带者中则无相应表现。结论MTHFR C677T多态性可导致血清Hcy水平增高和叶酸水平降低。在APOEε4非携带者中,MTHFR TT基因型可能增加aMCI的患病风险。

H型高血压急性缺血性脑卒中患者亚甲基四氢叶酸还原酶C677T基因多态性及其与肾功能的相关性

目的观察H型高血压急性缺血性脑卒中患者亚甲基四氢叶酸还原酶(MTHFR)C677T的基因多态性,分析其与H型高血压急性缺血性脑卒中患者肾功能的相关性。方法选择153例H型高血压急性缺血性脑卒中患者为观察组,同期158例非H型高血压急性缺血性脑卒中患者为对照组。两组均采集外周静脉血,采用PCR扩增和微阵列技术检测MTHFR C677T基因型,测算全身免疫炎症指数(SII),采用日立7600型全自动生化分析仪检测两组血清肌酐,据此测算肾小球滤过率(eGFR)。采用多元线性回归分析法分析MTHFR C677T基因型与H型高血压急性缺血性脑卒中患者同型半胱氨酸(Hcy)、eGFR的相关性,采用Spearman相关分析法分析SII与H型高血压急性缺血性脑卒中患者eGFR、Hcy的相关性。结果与对照组相比,观察组患者TT基因型分布频率最高,T等位基因频率最高(χ^(2)分别为19.188、5.138,P均<0.05)。观察组、对照组患者SII分别为583.54(384.97,903.73)、425.03(310.26,583.16),二者相比,P<0.05。与CC、CT基因型比较,TT基因型的H型高血压急性缺血性脑卒中患者血清Hcy水平高,eGFR水平低(F分别为28.544、3.749,P均<0.05)。MTHFR C677T TT基因型与H型高血压急性缺血性脑卒中患者血清Hcy呈正相关(β=4.173,P<0.05),与eGFR呈负相关(β=-6.559,P<0.05)。SII与H型高血压急性缺血性脑卒中血清Hcy水平呈正相关(r=0.226,P<0.05),与eGFR呈负相关(r=-0.129,P<0.05)。结论H型高血压急性缺血性脑卒中患者MTHFR C677T基因型主要为TT型。MTHFR C677T TT基因型的H型高血压急性缺血性脑卒中患者可能更易引起肾功能下降。

普通叶酸与活性叶酸补充对于MTHFR 677TT型不明原因反复流产患者红细胞叶酸水平的影响

目的·研究普通叶酸与活性叶酸补充对亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)677TT型不明原因反复流产(unexplained recurrent pregnancy loss,URPL)患者红细胞叶酸水平的影响。方法·选取2021年1—12月于北京大学第三医院生殖医学中心就诊的MTHFR 677TT型URPL患者45例。按照叶酸补充方式将其分为3组,包括A组16例(研究开始前尚未接受任何形式的叶酸补充,研究开始后进行活性叶酸补充),B组15例(研究开始前进行过普通叶酸的补充,研究开始后进行活性叶酸补充),以及C组14例(研究开始前进行过普通叶酸的补充,研究开始后进行普通叶酸与活性叶酸联合补充)。分别于入组时(第一次)、入组补充后(第二次)对3组患者的红细胞5-甲基四氢叶酸(5-methyltetrahydrofolate,5-MTHF)浓度进行检测,并开展比较。结果·在3组患者中,任意2组的第一次红细胞5-MTHF浓度间差异均无统计学意义。与第一次红细胞5-MTHF浓度相比,3组患者的第二次红细胞5-MTHF浓度均有提高(均P=0.000),且B组患者的红细胞5-MTHF浓度的增幅高于A组(t=2.373,P=0.049),但与C组间差异无统计学意义。结论·与补充普通叶酸相比,补充活性叶酸可以更好地在短时间内提高MTHFR 677TT型URPL患者的红细胞叶酸水平。

亚甲基四氢叶酸还原酶纯合突变的颅内静脉窦血栓一例并文献复习

目的总结亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)纯合突变致同型半胱氨酸(homocystine,Hcy)升高、诱发颅内静脉窦血栓形成(cerebral venous sinus thrombosis,CVST)的临床特点和诊疗过程。方法选取2023年1月3日解放军总医院第八医学中心的CVST患者1例,回顾性分析患者的临床、实验室资料,并复习既往相关文献。结果患者男,18岁,因“头痛伴恶心呕吐2 d”就诊,临床表现为头部持续胀痛,伴恶心呕吐,Hcy异常升高,影像学示上矢状窦、右侧横窦、乙状窦血栓形成,基因测序结果为MTHFR纯合突变。既往文献显示,MTHFR纯合突变与CVST无直接因果关系,但可导致Hcy水平升高,并间接增加CVST的风险。结论应重视CVST患者的Hcy检测,如发现Hcy无明显诱因的异常升高,应进一步完善CVST相关遗传因素的基因检测,尽早针对病因进行治疗。