MTHFR、PROC基因多态性与恶性肿瘤患者发生静脉血栓栓塞症的关联性分析

目的分析亚甲基四氢叶酸还原酶(MTHFR)、蛋白C(PROC)的基因多态性与恶性肿瘤患者发生静脉血栓栓塞症(VTE)的关联性。方法回顾性分析2023年11月14日至2024年2月14日新疆医科大学附属肿瘤医院收治的227例恶性肿瘤患者的临床资料,根据VTE发生情况将其分为VTE组(47例)和非VTE组(180例)。比较两组PROC基因(rs199469469位点)和MTHFR基因(rs1801133位点)多态性及其他临床资料,采用多因素logistic回归分析影响恶性肿瘤患者发生VTE的因素。结果VTE组D-二聚体水平以及有糖尿病史的人数比例高于非VET组,差异有统计学意义(P<0.05)。两组MTHFR基因rs1801133位点的基因型分布差异有统计学意义(P<0.05),VTE组MTHFR基因rs1801133位点的A等位基因频率显著高于非VET组[53.19%(50/94)vs 38.89%(140/360),χ^(2)=3.945,P=0.047]。两组PROC基因rs199469469位点的基因型比较差异无统计学意义(P>0.05)。多因素logistic回归分析结果显示,较高的D-二聚体水平[OR(95%CI)=1.436(1.213~1.696)]、有糖尿病史[OR(95%CI)=2.318(1.125~6.808)],以及MTHFR基因rs1801133位点的基因型为AA型[OR(95%CI)=1.927(1.459~3.751)]是促进恶性肿瘤患者发生VTE的独立危险因素(P<0.05)。结论MTHFR基因rs1801133位点多态性与恶性肿瘤患者发生VTE存在关联性,PROC基因rs199469469位点多态性与VTE发生的关联性不显著。

遵义地区汉族人群叶酸代谢能力基因MTHFR、MTRR基因多态性及与HPV感染的相关性分析

目的测定遵义地区汉族女性叶酸代谢能力基因MTHFR、MTRR基因型并分析其多态性,从基因水平评估叶酸代谢能力的风险程度,检测并分析HPV感染情况,并进一步探讨MTHFR、MTRR基因多态性与HPV感染的关系。方法收集1727例汉族女性全血标本及宫颈分泌物标本,磁珠法提取基因组DNA,实时荧光PCR技术进行MTHFR C677T、MTHFR A1298C、MTRR A66G基因型检测,采用卡方检验分析MTHFR、MTRR基因多态性分布,并与已报道的其他地区汉族女性数据进行比对;实时荧光PCR技术检测HPV分型,采用卡方检验分析HPV不同分组间MTHFR、MTRR基因型的分布差异。结果本研究纳入1727例遵义地区汉族女性MTHFR、MTRR基因多态性分布符合Hardy-Weinberg遗传平衡;遵义地区MTHFR C677T分布分别与塔城、准格尔旗、白银、枣庄、开封、郏县、南京、丹阳、福泉、长顺地区汉族女性MTHFR C677T基因分布差异均有统计学意义;遵义地区MTHFR A1298C分布仅与枣庄、开封、郏县3个北方城市以及福泉、长顺这2个南方城市的基因分布有差异;MTRR A66G基因分布仅与塔城地区的基因分布有差异。遵义地区汉族女性最常见的HPV感染亚型为HPV52。HPV阳性感染与HPV阴性组之间叶酸代谢能力风险差异无统计学意义。HPV阳性感染与HPV阴性组MTHFR的C677T的C等位基因与T等位基因与A1298C的A等位基因与C等位基因的分布差异无统计学意义;HPV阳性感染与HPV阴性组MTRR A66G的A等位基因与G等位基因的差异分布无统计学意义。结论遵义地区汉族女性人群叶酸代谢能力基因MTHFR C677T、MTHFR A1298C、MTRR A66G的基因多态性分布具有显著的地域特异性,HPV感染亚型也具有地域特征,HPV感染与叶酸代谢能力风险分布及MTHFR和MTRR基因多态性分布无相关性。

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。

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.

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.

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 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.

830例育龄妇女MTHFR基因A1298C位点多态性研究

目的探讨育龄妇女5,10-亚甲基四氢叶酸还原酶(MTHFR)基因A1298C位点基因多态性与年龄及民族是否有关,为指导育龄期妇女进行叶酸补充提供参考。方法采集2019年1月至2023年4月在该院门诊进行孕前或孕期行优生健康检查的汉族及其他民族的育龄女性外周血标本830例。采用PCR荧光探针法检测MTHFR基因A1298C位点的多态性,进行各年龄段及不同民族人群间基因多态性位点基因型分布比较。结果830例育龄期妇女中,MTHFR基因A1298C位点AA、AC及CC基因型频率分别为69.64%、27.35%和3.01%;各年龄段育龄女性MTHFR基因A1298C位点的基因型和等位基因频数和频率分布情况进行比较,差异均无统计学意义(P>0.05);汉族与藏族、回族、土族及蒙古族育龄女性间的MTHFR基因A1298C位点的基因型和等位基因频数和频率分布情况比较,差异均无统计学意义(P>0.05)。结论育龄妇女MTHFR基因A1298C位点多态性与年龄及民族无关,但有不同于其他地区的MTHFR基因A1298C位点多态性分布特征。

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。

重庆市主城区育龄期女性叶酸代谢酶MTHFR,MTRR基因多态性研究

目的:探讨重庆市主城区育龄期女性叶酸代谢酶基因多态性分布和叶酸利用风险等级特征。方法:回顾性分析2022年2月-2023年10月来本院检查的963名妇女基因检测结果。采用连接酶测序法对5,10-亚甲基四氢叶酸还原酶(MTHFR)基因c.677C>T、c.1298A>C位点和甲硫氨酸合成还原酶(MTRR)基因c.66A>G位点进行基因型检测,分析基因多态性,评估叶酸利用风险度。结果:MTHFR c.677C>TCC、CT及TT的基因型频率分别为53.1%、37.5%、9.4%,C、T等位基因频率分别为71.8%、28.2%;MTHFR c.1298A>C AA、AC及CC的基因型频率分别61.4%、34.3%及4.3%,A、C等位基因频率分别为78.5%、21.5%;MTRR c.66A>G AA、AG及GG的基因型频率分别52.9%、38.6%及8.5%,A、G等位基因频率分别为72.2%、27.8%。与其它地区相比,MTHFR c.677C>T、c.1298A>C基因多态性具有显著区域性差异,MTRR c.66A>G基因多态性区域性差异不明显。叶酸利用中度风险43.3%,高度风险9.7%。MTHFR c.677C>T和c.1298A>C连锁及单倍型分析两点分布存在连锁不平衡。结论:重庆市主城区育龄期妇女MTHRF、MTRR基因多态性分布具有区域性特点;叶酸利用中高度风险比例较高。

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.

MTHFR C677T基因多态性方法学比较

目的评价比较实时荧光定量PCR法与PCR-金磁微粒层析法两种方法检测5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性的一致性、检测限、特异性。方法随机选取首都医科大学附属北京天坛医院采集的50例静脉抗凝全血,均通过磁珠法提取基因组DNA,依照最新版分子诊断检验程序性能验证指南(CNAS-GL039)要求对两种方法学的一致性、检测限、特异性进行性能评价。结果实时荧光定量PCR与PCR-金磁微粒层析具有高度的一致性,采用两种方法检测50例样本的一致性为100%;两种方法检测交叉反应中检测结果未受影响,基因型之间无交叉污染情况;检测限验证中前者的灵敏度更高,最低检测限可达0.078125ng/μL,后者的最低检测限为0.625ng/μL。结论实时荧光定量PCR法与PCR-金磁微粒层析法均具有操作简便、灵敏度高,特异性强的特点,可用于人类MTHFR基因多态性检测,同时能够对叶酸代谢作出有效的诊断,需根据临床实验室的需求,选择合理有效的检测方法。

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.

Severe hyperhomocysteinemia due to MTHFR deficiency caused by a new mutation:A case report and literature review

Methylenetetrahydrofolate reductase(MTHFR)deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene,leading to a variety of clinical manifestations.In October 2022,the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders,presenting primarily with cognitive decline,limb tremors,abnormal mental and behavioral symptoms,seizures,and gait disturbances.These symptoms had gradually developed over 5 years,worsening significantly in the past year.The patient’s plasma homocysteine levels were 10 times higher than normal,and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei.Further genetic testing identified a paternal mutation c.1604G>A(p.R535Q)and a maternal mutation c.227T>G(p.L76R)of the MTHFR gene.After betaine supplementation,the plasma homocysteine levels decreased within a week,and the symptoms improved.The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency.The c.227T>G(p.L76R)mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency,but further research is needed to confirm its potential pathogenicity.Early treatment with betaine can fully reverse the symptoms.

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.