广西红水河流域长寿人群CETPTaqIB基因多态性、血脂水平及相关性分析

目的观察广西红水河流域长寿人群胆固醇酯转移蛋白(CETP)TaqIB基因的多态性,并探讨其基因型与该地区血脂水平和长寿的关系。方法应用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)方法对523例广西红水河流域90岁以上壮族长寿老人(长寿组)和498名普通健康壮族中老年人(对照组)进行基因分型,并检测血压、体质量、身高、体质量指数、CH、TG、HDL、LDL等指标。结果研究人群中CETPTaqIB的基因型频率分别为B1B1 38.49%,B1B2 49.95%,B2B2 11.56%,等位基因频率分别为B1 63.47%、B2 36.53%。两组CETP基因TaqIB位点的3种基因型及等位基因频率的分布无明显差异(P>0.05);长寿组CH、HDL、LDL水平显著高于对照组(P<0.05);长寿组基因型为B2B2和B1B2的HDL水平均明显高于基因型为B1B1者,长寿组B1B1携带者的HDL水平及各种基因型的LDL水平显著高于对照组,而各基因型的TG水平则明显低于对照组(P均<0.05)。结论 CETPTaqIB的基因多态性与血脂水平关系密切,可能是红水河地区长寿的分子遗传学基础之一。     

亚甲基四氢叶酸还原酶基因多态性与原发性高血压患者合并冠心病的相关性研究

目的探讨N5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T位点突变与河南豫北地区原发性高血压及其合并冠心病发病的关系。方法选择原发性高血压患者405例为高血压组,高血压合并冠心病患者400例为冠心病组,健康体检者400例为对照组。对3组MTHFR基因C677T多态性进行基因分型。结果冠心病组T等位基因频率和TT基因型频率明显高于高血压组和对照组(P<0.05)。冠心病组TT基因型患者TC和血浆同型半胱氨酸水平明显高于CC+CT基因型(P<0.05)。结论 MTHFR基因C677T多态性与原发性高血压患者冠心病的发生相关。     

血管紧张素原基因T704C多态性与血脂水平及原发性高血压的相关性探讨

采用PCR-RFLP方法检测开滦煤矿汉族人群（1224例）血管紧张素原（AGT）基因,1704C单核苷酸多态性;用全自动生化分析仪测定血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、极低密度脂蛋白（VLDL）水平,分析AGT基因T704C多态性与血脂水平及原发性高血压（EH组）的相关性。结果非EH（NEH组,1004例）携带CC基因型者血清TG、VLDL水平显著高于携带TT、TG者,携带TT基因型者HDL水平高于携带TC和CC基因型者（P均〈0．05）;EH组携带TT基因型者TC、TG、VLDL水平高于NEH组,HDL含量低于NEH组,携带TC基因型者TC、TG、LDL、VLDL水平高于NEH组,P均〈0．05。认为AGT基因T704C多态性与EH发病有关,可能机制为影响血脂水平。     

N5，N10-亚甲基四氢叶酸还原酶基因多态性及血浆同型半胱氨酸与冠心病的关系

目的研究N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性、血浆同型半胱氨酸(Hcy)与冠心病的关系。方法选取2013年至2015年在我院住院的冠心病患者256例,按年龄分为60岁组(中青年组)107例及≥60岁组(老年组)149例,选取同期行健康体检的人群145例作为对照组,应用聚合酶链反应(PCR)技术和基因芯片分析技术检测MTHFR基因C677T多态性,应用高效液相色谱法测定血浆Hcy水平,分析不同组群之间MTHFR基因C677T多态性的分布及Hcy水平。结果 MTHFR基因分布频率:中青年组CC型、CT型、TT型基因频率分别为26.2%,43.9%,29.9%,C等位基因频率为48.1%,T等位基因频率为51.9%。中青年组CC型、CT型、TT型基因频率分别为35.6%,42.3%,22.1%,C等位基因频率为56.8%,T等位基因频率为43.2%。对照组CC型、CT型、TT型基因频率分别为37.9%,40.1%,21.4%,C等位基因频率为58.3%,T等位基因频率为41.7%。中青年组T等位基因频率明显高于对照组(χ~2=5.10,P=0.015),中青年组Hcy浓度明显高于对照组。老年组T等位基因频率与对照组比较差异无显著性(χ~2=0.147,P=0.382),两组间Hcy浓度差异无显著性。各组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者(P0.01),而后两者间差异无显著性。结论 MTHFR基因TT型可导致Hcy水平明显升高,MTHFR基因C677T点突变仅与中青年组冠心病患者相关,与老年组冠心病患者无明显相关,Hcy水平升高及MTHFR基因T等位基因频率增高可能为中青年冠心病患者的危险因素,提示不同年龄阶段的冠心病患者发病的机制可能存在差异。     

亚甲基四氢叶酸还原酶677C→T及1298A→C基因多态性与糖尿病心血管病变的相关性

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与糖尿病心血管并发症(DC)的关系. 方法应用PCR-RFLP法检测84例健康人(NC)和158例2型糖尿病患者[分为无DC(NDC)和DC组]的MTHFR677C→T及1298A→C基因多态性,比较各组间基因型分布和等位基因频率. 结果 DC组MTHFR677 TT基因型分布及T等位基因频率均高于NC或NDC组,且叶酸水平较低(P<0.001); 各组间MTHFR1298A→C基因型分布及等位基因频率差异无统计学意义(P>0.05);MTHFR基因型、年龄是DC的危险因子. 结论 MTHFR677C→T突变与DC的发生有关.     

MTHFR基因多态性与河南中部地区汉族人群急性冠脉综合征发生的关联性研究

目的探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与河南中部地区汉族人群急性冠脉综合征(ACS)发生的关联性。方法招募河南中部地区汉族ACS患者280例作为观察组,选取同期行健康体检的河南中部地区汉族健康受试者286名作为对照组。采用荧光染色原位杂交技术检测两组MTHFR基因C677T、A1298C位点基因型,比较两组受试者各基因型及等位基因分布的差异,采用二元Logistic回归分析MTHFR基因多态性与ACS发生的关联性。结果两组各基因型分布频率均符合Hardy-Weinberg平衡(P0.05)。对照组MTHFR C677T位点CC、CT、TT型分布频率分别为31.82%、47.90%、20.28%,MTHFR A1298C位点AA、AC、CC型分布频率分别为73.78%、21.68%、4.54%;观察组MTHFR C677T位点CC、CT、TT型分布频率分别为16.43%、40.71%、42.86%,MTHFR A1298C位点AA、AC、CC型分布频率分别为69.29%、27.14%、3.57%。两组受试者MTHFR C677T各基因型分布频率及等位基因频率比较差异有统计学意义(P0.05),而MTHFR A1298C各基因型分布频率及等位基因频率比较差异无统计学意义(P0.05)。二元Logistic回归分析显示,MTHFR C677T基因型是ACS发生的影响因素(P0.05),以TT型为参照,CC型发生ACS的可能性是TT型的24.4%,CT型发生ACS的可能性是TT型的40.2%。结论 MTHFR基因多态性与河南中部地区汉族人群ACS发生有关,其中C677T位点突变可能是ACS发生的影响因素,而A1298C位点基因多态性与ACS发生的关联性较低。     

MTHFR C677T基因多态性与冠心病患者同型半胱氨酸及冠脉狭窄程度的相关性

[摘 要] 目的 探讨MTHFR C677T基因多态性与河南中部汉族冠心病（CHD）患者同型半胱氨酸(Hcy)及冠脉狭窄程度的相关性。方法 应用荧光染色原位杂交技术对河南中部汉族352例CHD患者和340例非CHD对照者进行MTHFR C677T基因多态性检测,并比较两组不同基因型之间Hcy水平的差异。采用Gensini评分系统评价CHD患者的冠脉狭窄程度,多元线性回归分析法探讨MTHFR C677T基因多态性以及其他因素与Gensini得分之间的相关性。结果 非CHD组MTHFR C677T 基因CC、CT、TT 型例数及分布频率分别为113(33.2％)、159(46.8％)、68(20％),CHD组MTHFR C677T位点CC、CT、TT型例数及分布频率分别为85(24.1％)、157(44.6％)、110(31.3％)。两组受试者各基因型分布频率均符合Hardy-Weinberg 平衡（P＞0.05）。两组受试者MTHFR C677T各基因型分布频率及等位基因频率比较,差异均有统计学意义（P＜0.001）。CHD组血清Hcy水平、高血压、糖尿病患病率分别为（23.1±8.7）、27.8%和16.8%,均高于非CHD组的（18.6±7.4）、10.6%和6.2%,差异均有统计学意义（P <0.05）。两组不同基因型之间血清Hcy水平差异有统计学意义（P <0.05）。多元线性回归分析结果显示,MTHFR C677T基因多态性与Gensini得分的相关性无统计学意义（β=-0.16,95%CI：-0.21～0.18,P=0.785）。结论MTHFR C677T基因多态性影响Hcy水平,但与CHD患者冠脉狭窄程度无明显相关性。     

高血压患者亚甲基四氢叶酸还原酶基因C677T多态性与血脂异常的相关性

目的探讨血浆同型半胱氨酸(Hcy)及其代谢关键酶亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与中国汉族人群原发性高血压患者血脂异常的关系。方法选取原发性高血压患者312例,女性134例,男性178例,平均年龄58.25岁,收集患者基本资料,检测血浆Hcy、血脂、空腹血糖(FBG)、尿酸(UA)等临床生物化学指标。应用Taqman探针技术检测患者MTHFR C677T基因分型。根据2007年中国成人血脂异常防治指南,将入选的312例原发性高血压患者分为血脂异常组194例和血脂正常组118例,同时将血脂异常组分为4个亚组:高胆固醇血症组54例,高甘油三酯血症组53例,混合型高脂血症组59例,低高密度脂蛋白血症组22例,并进行亚组分析。结果血脂异常组体质指数(BMI)、FBG、UA高于血脂正常组(P0.01)。血脂异常组MTHFR C677T的CC、CT、TT三种基因型频率和C、T两种等位基因频率与血脂正常组比较差异无统计学意义(P0.05),血脂异常各亚组之间的基因型频率、等位基因频率差异无统计学意义,与血脂正常组之间差异亦无统计学意义。MTHFR C677T不同基因型间四项血脂水平均无统计学差异,但TT基因型者Hcy水平高于CT、CC基因型者(P0.05),而CT基因型者Hcy水平与CC基因型者比较差异无统计学意义(P0.05)。高密度脂蛋白胆固醇(HDLC)水平与Hcy水平呈负相关(r=-0.116,P0.05),但是在校正了年龄、BMI、UA、FBG后此相关性消失;总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)水平与Hcy水平无相关性(P0.05)。Logistic回归分析显示,在校正了BMI、FBG、UA后基因型与血脂异常无相关性(P0.05)。结论在原发性高血压患者中MTHFR C677T基因多态性与血脂异常无关联,而与Hcy呈显著相关。血脂异常与FBG、UA、BMI有关,而与Hcy无关,但HDLC与血浆Hcy水平呈负相关。     

MTHFR基因多态性与肺血栓栓塞症的关系

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与肺栓塞的关系。方法选取肺栓塞患者102例及同期住院或门诊患者及健康体检者120例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行检测两组MTHFR基因C677T、A1298C位点的多态性,比较两组基因型和等位基因分布频率。结果 1在肺栓塞组中,MTHFR C677T位点CC、C/T、TT基因型频率分别为20.6%、31.4%、48%,在对照组中分别为29.2%、39.1%、31.7%,在两组中TT基因型频率差异有统计学意义(P=0.013)。在两组间,T等位基因分布频率差异有统计学意义(P=0.008)。2在肺栓塞组中,MTHFR A1298C位点AA、A/C、CC基因型频率分别为23.5%、31.4%、45.1%,在对照组中分别为31.7%、37.5%、30.8%,在两组中CC基因型频率差异有统计学意义(P=0.029),等位基因C分布频率两组间差异有统计学意义(P=0.018)。结论MTHFR基因C677T位点的TT基因型及A1298C位点的CC基因型多态性可能为肺血栓栓塞症的高危因素。     

长治老年人群血浆同型半胱氨酸水平与MTHFRC677T基因多态性

目的探讨长治地区健康老年人群血浆同型半胱氨酸(HCY)水平与N5,N10-亚甲基四氢叶酸还原酶(MTHFR)C677T基因位点的基因多态性。方法采用酶联免疫吸附法进行血浆HCY水平测定;采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)对MTHFR C677T进行基因多态性分析。结果长治地区健康老年人群血浆HCY水平为(11.0±3.1)μmol/L,与健康青年人群相比,无统计学差异(P0.05)。老年人群中MTHFR C677T基因的CC、CT和TT基因型频率分别为15.38%、48.72%和35.90%,与青年人群相比,两者差异无统计学性(P0.05);老年人群C、T等位基因频率分别为39.74%和60.26%,与青年人群相比,两者差异无统计学意义(P0.05)。MTHFR C677T基因型频率在长治地区健康老年人群、青年人群中均符合Hardy-Weinberg平衡。健康老年人群MTHFR C677T位点各基因型间,血浆HCY水平亦无显著差异。健康老年人群、青年人群TT基因型血浆HCY水平差异显著(P0.05)。结论长治人群MTHFR C677T纯合突变基因型频率高,且老年人群TT基因型血浆HCY水平显著高于青年人群。     

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     

Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease.

Mild hyperhomocysteinemia is associated with homozygosity for the thermolabile variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) and could increase the risk of venous thromboembolic disease (VTD). Recently, the second A1298C mutation of the MTHFR gene was described. The present study aimed to analyze both mutations of the MTHFR gene and plasma homocysteine levels in subjects with VTD. The study groups comprised 146 patients with VTD and 100 healthy subjects. There were no statistical differences in carrier frequency and allelic frequency for both A1298C and C677T mutations, nor were there any differences encountered between subjects with VTD and controls in either plasma homocysteine levels or according to C677T or A1298C genotypes of MTHFR. In our VTD patients and controls, neither MTHFR 677CT/1298CC nor MTHFR 677TT/1298CC combined genotypes were observed; double heterozygotes (A1298C/C677T) were represented only in 11% of VTD patients, and in 15% of the controls. In conclusion, the polymorphisms C677T and A1298C of MTHFR and fasting plasma homocysteine levels do not seem to be significant risk factors for venous thromboembolic disease.     

MTHFR C677T基因多态性与新疆哈族和汉族食管癌易感性的关系

目的:探讨亚甲基四氢叶酸还原酶(MTHFR) 基因C677T多态性与新疆哈族、汉族食管癌易感性的关系．方法:用PCR-RFLP方法检测食管癌患者178 例(哈萨克族94例,汉族84例)和同一地区无肿瘤病史的正常对照者155例(哈萨克族98例,汉族57例)的MTHFR基因C677T基因型分布．结果:新疆哈族食管癌组中MTHFR C677T 3种基因型CC,CT,TT,所占比例分别是 56．4％,36．2％,7．4％,与新疆汉族食管癌组中的32．9％,40．0％,27．1％相比,存在显著差异(X2=1 5．37,P<0．05);哈族正常对照组分别为58．2％,29．6％,12．2％与汉族正常对照组 22．8％,52．6％,24．6％相比,有显著差异(X2= 18．26,P<0．05)．MTHFR 3种基因型在哈族食管癌组中的分布(CC 56．4％,CT 36．2％and TT 7．4％)与对照组中(CC 22．8％,CT 52．6％and TT 24．6％)相比,无显著差异(X2=1．776,P= 0．412)．在汉族食管癌组与对照组间也无显著差异(X2=2．750,P=0．253)．结论:MTHFR C677T基因多态性分布在新疆哈族、汉族正常对照组间存在民族差异,在食管癌间也存在差异．MTHFR C677T基因多态性可能与新疆哈萨克族与汉族食管癌的易感性无关．     

Associations of methylenetetrahydrofolate reductase C677T genotype with blood pressure levels in Chinese population with essential hypertension

Objective: To confirm the association between baseline blood pressure (BP) levels and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients with essential hypertension. Methods: A total of 347 patients were enrolled from the Dongzhi community in Anhui Province, China. The C677T polymorphism of the MTHFR gene was detected using high-throughput TaqMan allelic discrimination assay. Baseline BP was measured using a standardized mercury-gravity monometer. Results: In the whole sample, the frequency of the MTHFR C677T genotypes CC, CT, and TT were 38.6%, 48.1%, and 13.3%, respectively. In a recessive model (CC+CT versus TT genotypes), baseline diastolic blood pressure (DBP) was significantly higher in patients with the TT genotype compared to those with the CT or CC genotypes (P= 0.013). We also divided all patients into three groups based on the tertiles of the baseline BP distribution. Compared to subjects in the lowest tertile of DBP, the adjusted odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI: 1.1 to 6.2). However, no significant associations were observed between baseline systolic blood pressure (SBP) and the MTHFR C677T polymorphism. Conclusions: The MTHFR gene polymorphism could be an important genetic determinant of baseline DBP levels in Chinese essential hypertensive patients.     

Dietary factors and biomarkers involved in the methylenetetrahydrofolate reductase genotype-colorectal adenoma pathway

BACKGROUND & AIMS: Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate homeostasis and metabolism. We assessed 2 polymorphisms in the MTHFR gene (C677T and A1298C) in relation to colorectal adenoma recurrence and conducted analyses to investigate their joint effects with plasma and dietary markers of folate status. METHODS: We prospectively analyzed data from 1598 individuals genotyped for the C677T polymorphism and 1583 with data on A1298C. RESULTS: Among nonusers of multivitamin supplements, compared with wild-type carriage, higher odds of recurrence were observed for those with the 677 TT variant (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.04-2.63) and a nonsignificant increase was observed among those with the 1298 CC variant (OR, 1.50; 95% CI, 0.93-2.40). Diplotype analyses among nonusers of multivitamins showed that individuals who carry the MTHFR 677TT_1298AA or 677CC_1298CC combination were significantly more likely to have a recurrence compared with those with the double wild-type (OR, 2.05 for TT_AA and 1.85 for CC_CC). Higher odds of recurrence were observed among participants with low folate intake or plasma folate and the 677 TT or 1298 CC variants compared with those with lower levels and the wild-type or heterozygous genotypes. Stronger associations were shown for the combination of high homocysteine and the 677 TT variant (OR, 2.29; 95% CI, 1.00-5.26) but not the 1298 CC variant (OR, 1.09; 95% CI, 0.39-3.01). CONCLUSIONS: We propose that the effect of the MTHFR genotypes on increasing risk of adenoma recurrence in the presence of a low folate status is through their increase in homocysteine concentrations, which in turn could result in DNA hypomethylation via pathways involving S-adenosylhomocysteine.     

MTHFR基因多态性与冠心病的关系

目的研究天津地区人群N^5,N^10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与冠心病的关系。方法应用聚合酶链反应（PCR）技术和限制性酶切片段长度多态性（RFLP）分析技术检测50例冠心病患者（冠心病组）和50例正常人（对照组）的MTHFR基因C677T多态性,应用高效液相色谱法测定血浆同型半胱氨酸（Hcy）水平,采用125I标记放免法测定血清叶酸浓度。结果1.冠心病组与对照组MTHFR基因频率分布不同（P〈0.05）,对照组CC型、TC型、TT型基因频率分别为52.0%,28.0%,20.0%,冠心病组分别为26.0%,44.0%,30.0%。冠心病组T等位基因频率为52.0%,C等位基因频率为48.0%,与对照组比较有显著性差异（P〈0.05）。2.两组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者（P〈0.05）,而后两者间无显著性差异（P〉0.05）。3.冠心病组Hcy浓度高于照组（P〈0.05）,两组叶酸水平无显著性差异（P〉0.05）,血浆Hcy浓度与叶酸水平呈显著负相关（r分别为-0.617和-0.588,P〈0.05）。结论MTHFR基因C677T点突变与冠心病发病密切相关,MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素。     

Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients

The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC.     

Interaction between Mediterranean diet and methylenetetrahydrofolate reductase C677T mutation on oxidized low density lipoprotein concentrations: the ATTICA study

BACKGROUND: The oxidative modification of low-density lipoprotein (LDL) has been suggested to be a key element in atherogenesis, while methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been associated with the development of coronary heart disease. We evaluated whether adoption of a Mediterranean type of diet is associated with oxidized LDL levels, as well as the role of MTHFR C677T mutation in this relationship. METHODS: We studied demographics, lifestyle, clinical, biochemical and genetic data from 322 men (46+/-13 years) and 252 women (45+/-14 years), without any clinical evidence of cardiovascular disease, from the Attica region, Greece (i.e. the ATTICA study). Among the other parameters we also measured oxidized (ox)-LDL levels, and the distribution of MTHFR. Adherence to the Mediterranean diet was evaluated by a special diet score. RESULTS: The distribution of MTHFR genotypes was: 41% for homozygous normal (CC) genotype, 48% for heterozygous (CT) and 11% for homozygous mutant (TT) genotype. Ox-LDL levels were higher in TT as compared to CC and CT (70.8+/-26 vs. 51.0+/-26 vs. 63.7+/-24 mg/dl, p<0.001). Greater adherence to the Mediterranean diet was inversely associated with ox-LDL levels (standardized beta=-0.34, p<0.001), after controlling for several confounding variables; however, stratified analysis revealed that adherence to the Mediterranean diet was associated with lower ox-LDL levels in TT and CT individuals (standardized beta=-0.67, p=0.001 and standardized beta=-0.66, p=0.025, respectively), but not in CC (standardized beta=-0.18, p=0.10), after controlling for several potential confounders. CONCLUSION: The observed gene-to-diet interaction on ox-LDL concentrations may provide a pathophysiological explanation by which a Mediterranean type of diet could influence coronary risk in people with increased oxidative stress.     

Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07) and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6 vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/μl was slower for patients with the 677TT genotype than for patients with other genotypes (677TT, 59 days; 677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T polymorphism on treatment-related mortality (TRM) were also analyzed. One-year cumulative TRMs for patients with the TT genotype and the other genotypes were 66 and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56% (p=0.11). No association was observed between the A1298C polymorphism and clinical outcome for any of the different genotypes. Therefore, patients at high risk of developing hepatic toxicity and with a poor likelihood of survival could be selected by genotyping MTHFR C677T before allogeneic stem cell transplantation.     

The association between 5, 10 – methylenetetrahydrofolate reductase and the risk of unexplained recurrent pregnancy loss in China: A Meta-analysis

Backgroud:To analyze the correlation between gene polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR) and risk of unexplained recurrent pregnancy loss (URPL) in Chinese women.Methods:Eligible studies were searched in Pubmed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Established inclusion criteria were used to screening articles, subsequently evaluate the quality of the included studies, Stata 16.0 PM and RevMan 5.3 software were conducted for meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between MTHFR and risk of URPL in Chinese women.Results:For MTHFR C677T, fifty studies were included, involving 6677 URPL cases and 8111 controls. The overall results showed that MTHFR C677T was significantly correlated with URPL risk, especially in the homozygous model (TT vs CC; OR 3.06; 95% CI 2.56–3.66). For MTHFR A1298C, twenty-first studies were included, involving 3439 URPL cases and 3155 controls. The results showed that MTHFR A1298C was also significantly correlated with URPL risk in recessive (CC vs AC + AA; OR 1.55; 95% CI 1.25–1.93) and homozygous (CC vs AA; OR 1.53; 95% CI 1.22–1.91) models. In addition, sub-group results showed that no significant difference between north and south China populations in the MTHFR gene polymorphisms and URPL risk. Of note, the patients carrying MTHFR C677T and MTHFR A1298C joint mutants had no synergistic effect (OR 2.71; 95% CI 0.84–8.70) on the occurrence of URPL compared with the wild-type homozygous genotype (MTHFR 677CC/ MTHFR 1298AA).Conclusion:Studies included in this meta-analysis suggested that MTHFR 677T allele and 677TT genotype and MTHFR 1298CC genotype were both associated with URPL; testing MTHFR C677T gene polymorphism was a more appropriate target compared with other mutations in the prediction of URPL.