Methylenetetrahydrofolate reductase gene polymorphisms in Burkina Faso: impact on plasma fasting homocysteine and after methionine loading test

In Burkina Faso the levels of plasma homocysteine (Hcy) are lower and the methionine loading tests suggest a more effective Hcy metabolism. The polymorphisms of methylenetetrahydrofolate reductase (MTHFR) showed a relevant difference in the allele frequencies of T MTHFR-677 in young and in old subjects, while the allele frequency of C MTHFR-1298 was comparable in young and old subjects. The aim of this paper was to study the impact of the MTHFR polymorphisms on plasma fasting Hcy and after methionine loading in Burkina Faso. The young subjects with CC MTHFR-677 genotype had levels of Hcy significantly lower than CT and TT subjects. The level of Hcy in subjects who had AA, AC and CC MTHFR-1298 genotypes were comparable. The levels of Hcy after the methionine loading test were significantly higher in CT and TT MTHFR-677 genotype. These results suggest that the genetic situation in Burkina Faso is different from that of other Western countries and this guarantees the maintenance of lower plasma levels of Hcy in young and old Africans. The elevated levels of plasma Hcy in old subjects compared to young subjects, against the low prevalence of the T allele in elderly subjects, is discussed.     

亚甲基四氢叶酸还原酶基因多态性与深静脉血栓形成

目的　研究血浆同型半胱氨酸 (Hcy)水平及亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与深静脉血栓形成 (DVT)的关系。方法　采用聚合酶链反应 限制性片段长度多态性法检测 10 1名健康对照者和 6 9名DVT患者的MTHFRC6 6 7T基因型 ,采用荧光偏振免疫法 (FPIA)测定血浆Hcy水平。结果　DVT组MTHFRC6 77T的TT基因型频率 (2 0 3% )高于对照组 (11 9% ) ,但两者差异无显著意义 (P >0 0 5 ) ,TT基因型不增加DVT患病的危险性 [比数比 (OR) =0 5 3,95 %可信限 (CI) 0 2 2 8～1 2 2 8]。DVT组的血浆Hcy水平为 (12 2± 8 7) μmol/L明显高于对照组的 (10 4± 4 8) μmol/L(P <0 0 5 ) ,轻度升高的同型半胱氨酸水平增加了DVT患病的危险性 (OR =2 5 3,95 %CI 1 0 4 9～ 6 0 5 )。两组人群MTHFRC6 77T的TT型血浆Hcy水平分别为 (19 7± 15 3) μmol/L和 (17 2± 7 8) μmol/L均明显高于同组CC型和CT型的血浆Hcy水平 (P <0 0 5 )。结论　轻度升高的同型半胱氨酸水平是我国北方地区汉族人DVT发病的独立危险因子 ,MTHFR基因C6 6 7T多态性可能与DVT无关联     

亚甲基四氢叶酸还原酶基因突变与心脑血管梗死发生的关系

目的　研究同型半胱氨酸(HCY)水平及其代谢相关酶亚甲基四氢叶酸还原酶(MTHFR)基因突变与心脑血管梗死的关系。方法　采用酶联免疫试剂盒测定同型半胱氨酸水平,聚合酶链反应-限制性片段长度多态性(PCR RFLP)法检测 MTHFR基因中 C677T基因型。结果　心肌梗死组HCY水平为(21.93±11.58)μmol/L,脑梗死组HCY水平为(21.79±11.15)μmol/L;对照组HCY水平为(15.49±10.34)μmol/L,心脑梗死组HCY水平显著高于对照组,P<0.01。MTHFR基因C677T心肌梗死组TT、TC、CC型频率分布分别为 47%、27%、12%,与对照组有显著差异,P<0.05; MTHFR基因C677T脑梗死组TT、TC、CC型频率分布分别为 51%、28%、14%,与对照组有显著差异,P<0.05。两两比较中,病例组的 TT 型、TC型 HCY 水平显著高于 CC 型。结论　高HCY血症是心脑梗死发生的危险因素,MTHFR基因 C677T突变是高 HCY血症的原因,MTHFR基因C677T突变是易发心脑血管梗死的一种内在危险因素。     

Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke.

The 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene 677C --> T polymorphism causes an A222V amino acid change which affects MTHFR enzyme activity and can increase homocysteine, a vascular disease risk factor. This polymorphism was examined for association with stroke. In a case-control study of 241 ischemic stroke patients and 304 controls in Hong Kong, the V allele increased in stroke [28% vs. 20%, odds ratio (OR) 1.5, p=0.003]. A lack of significance for the increase in the VV genotype (7.5% vs. 4.6%, OR 1.7, p = 0.16) may be due to its rarity in this region. V -allele carriers had more severe strokes (according to the NIH stroke scale). The association of the V allele with stroke occurred mostly in women or older subjects and was due to decreasing V allele frequency with age, as seen in other studies. This V frequency decline with age might be due to a loss of V -carrying controls from a higher risk of cancer, vascular disease, bone fracture, and kidney failure when folate is sparse. Examination of previous studies revealed that the association of VV genotype with stroke appeared stronger in Japan than elsewhere, possibly due to dietary differences. Perhaps folate supplementation for stroke prevention would particularly benefit VV individuals in such high-risk regions.     

赣南地区亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性分析

目的通过检测赣南地区亚甲基四氢叶酸还原酶(MTHFR)C677T基因型,分析该地区该基因多态性构成频率,以此来指导该地区人群叶酸治疗。方法采用荧光定量PCR方法,以2017年5月-2018年3月来我院就诊的1787例患者为研究对象,统计分析该地区MTHFR(C677T)基因型频率。结果该地区该基因CC型占39.79%,CT型占43.65%,TT型占16.68%。该地区不同县比较无统计学差异(P>0.05);与已报道的山东、河南等省份比较有统计学差异(P<0.05)。结论赣南地区MTHFRC677T基因多态性分布无县域差异性,以CT为主;与北方地区比较有地域差异性。     

Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age

BACKGROUND: Elevated fasting levels of total homocysteine are now accepted as an independent risk factor for the development of arteriosclerotic vascular diseases. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), caused by the C677T point mutation, leads to increased thermolability of the enzyme, with reduced enzyme activity. We studied the frequency of this mutation in different groups of the Swiss adult population. PATIENTS AND METHODS: DNA from 361 subjects was screened for the thermolabile MTHFR variant with PCR. Included were healthy subjects without vascular disease (n = 118), older healthy subjects (n = 106), patients with coronary artery disease (CAD, n = 75), and patients with peripheral arterial occlusive disease (PAOD, n = 63). RESULTS: In the different groups studied, homozygosity for the mutation ranged from 4.8 to 16.2%, with a frequency of 16.2% in the healthy cohort. The allele frequencies of the thermolabile allele were 38.5 and 27.3 in young and old controls, and 37.3 and 33.3 in CAD and PAOD patients. In the healthy younger subjects the mutant allele was 1.4 times more frequent compared to the older subjects (P = 0.01). No difference in either MTHFR genotype distribution (P = 0.33) or allele frequencies (P = 0.48) between patients and controls was found. Except for the PAOD group with elevated tHcy levels for the +/+ carriers compared to the other genotypes, no statistically significant difference was found comparing homocysteine levels with genotype. CONCLUSION: This study shows no link between the mutation and the occurrence of vascular disease but we found evidence pointing to a correlation between the mutation and longevity in our population.     

Elevated levels of plasma homocysteine in postmenopausal women in Burkina Faso.

BACKGROUND: Low levels of plasma homocysteine have been found in children and adult populations living in Burkina Faso in association with a low prevalence of coronary heart disease. METHODS: Based on this finding, the levels of plasma homocysteine and other thiols (cysteine, cysteinylglycine, glutathione) in postmenopausal women living in Burkina Faso were evaluated with the aim of investigating whether age and life conditions influence plasma homocysteine and other thiol levels. RESULTS: It was found that in older postmenopausal women the mean level of homocysteine was higher (16.4+/-6.6 micromol/L) than in fertile women (6.8+/-1.2 micromol/L) and that this increase was correlated with cysteine levels (166.6+/-44.6 micromol/L). While the glutathione level in postmenopausal women was lower (3.6+/-2.3 micromol/L) compared with fertile women (7.0+/-1.7 micromol/L), cysteinylglycine levels were within the normal range (29.9+/-9.3 micromol/L). No correlation was found between homocysteine levels and serum folate, vitamin B(12), vitamin B(6), cystatin C and serum creatinine levels. The older the women were, the higher were their plasma homocysteine levels: levels up to 20.2+/-9.1 micromol/L were found in those >70 years old. CONCLUSIONS: The elevated levels of homocysteine in the postmenopausal women of Burkina Faso must be viewed as a characteristic of older age and its metabolic consequences.     

亚甲基四氢叶酸还原酶基因A1298C多态性与帕金森病易感性的Meta分析

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因A1298C位点单核苷酸多态性(SNP)与帕金森病(PD)易感性的关联情况。方法通过中国生物医学文献数据库、中国期刊网全文数据库、万方数据库、维普信息资源系统,Pub Med、Cochrane Library、Ovid SP、Wiley Online Library、Springer Link、EBSCO、Elsevier Science Direct、Google scholar数据库检索MTHFR基因A1298C位点SNP与PD相关的病例对照研究,利用Rev Man 5.3和Stata 12.0软件,根据异质性大小选用随机效应或固定效应模型对各研究数据进行分析。结果共纳入8篇文献。Meta分析结果提示PD组和对照组AA基因型[OR=0.92,95%CI:0.78~1.09,P=0.33]和CC基因型[OR=1.19,95%CI:0.89~1.59,P=0.23]、A等位基因[OR=0.92,95%CI:0.81~1.04,P=0.19]和C等位基因[OR=1.09,95%CI:0.96~1.24,P=0.19]差异均无统计学意义。结论 MTHFR基因A1298C位点SNP与PD易感性无关联性。     

亚甲基四氢叶酸还原酶C677T基因多态性与2型糖尿病合并冠心病的关系

目的 研究同型半胱氨酸代谢关键酶亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因C677T多态性与糖尿病合并冠心病发病的关系,探讨MTHFR是否为糖尿病合并冠心病的易感基因。方法 研究对象包括105名糖尿病合并冠心病的患者（合并组）、88名单纯糖尿病患者（糖尿病组）和91名健康人。应用聚合酶链反应-限制性内切酶长度多态性方法（PCR—RFLP）检测MTHFR C677T基因多态性,同时检测血浆同型半胱氨酸（homocysteine,Hcy）、叶酸、维生素B12、各种血脂。结果 合并组与糖尿病组比,等位基因频率差异有统计学意义（Х^2=6．8,P〈0．05）,合并组T等位基因的OR值为1．638（95％ CI,1．082～2．479）,基因型频率差异亦有统计学意义（Х^2=5．481,P〈0．05）。Logistic回归分析显示MTHFR 677携带T基因（CT＋TT）的OR值为2．68（95％ CI,1．233—5．824）。结论 MTHFR 677携带T基因与2型糖尿病合并冠心病发生独立相关。检测MTHFR 677位点基因特点可能为糖尿病合并冠心病的预防以及个体化治疗提供新思路、新方法。     

Methylenetetrahydrofolate reductase C677T gene polymorphism and the association with dyslipidemia in type 2 diabetic Palestinian patients

BackgroundDyslipidemia in diabetes is common and characterized by hypertriglyceridemia with decreased levels of high‐density lipoprotein. The objective of this study was to assess the prevalence of MTHFR C677T polymorphism in Palestinian T2DM patients and to investigate the association between this polymorphism and lipid profile in diabetic patients with and without dyslipidemia.MethodsA total of 208 T2DM patients including 98 with dyslipidemia and 110 without dyslipidemia were enrolled in this study. The MTHFR C677T genotyping was conducted by PCR‐RFLP followed by agarose gel electrophoresis.ResultsThere were no significant differences in either the genotype distribution or allele frequency in T2DM patients with or without dyslipidemia (37.8% CC, 54% CT, 8.2% TT vs. 48.2% CC, 41.8% CT, 11% TT; p = 0.209). However, among the dyslipidemic group, the TT carriers have a higher HDL level (46.8 ± 17.8) compared to (CC+CT) carriers (34.68 + 11.9) (p = 0.01). In the group without dyslipidemia, there was a significant elevation in diastolic blood pressure (DBP) among the CC carriers (83.6 ± 10.6) compared to those who carried at least one mutant allele (CT+TT) (78.1 ± 11.1) (p = 0.009).ConclusionsThe study shows that in our Palestinian population the MTHFR 677TT genotype lowers DBP significantly in patients without dyslipidemia and is related to increased level of HDL in diabetic dyslipidemia patients.     

Real-time PCR for dihydrofolate reductase gene single-nucleotide polymorphisms in Plasmodium vivax isolates

Mutations in the dhfr gene of Plasmodium vivax (pvdhfr) are associated with resistance to the antifolate antimalarial drugs. Polymorphisms in the pvdhfr gene were assessed by hybridization probe technology on the LightCycler instrument with 134 P. vivax-infected blood samples from Turkey (n = 24), Azerbaijan (n = 39), Thailand (n = 16), Indonesia (n = 53), and travelers (n = 19). Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117N) in the pvdhfr genes were found in all Thai samples (100%). pvdhfr mutant-type alleles were significantly more common in samples from travelers (42%) than in those from patients from Indonesia (5%). Surprisingly, the pvdhfr single-mutation allele (S117N) was identified at a high frequency in parasites from Turkey and Azerbaijan (71 and 36%, respectively), where sulfadoxine-pyrimethamine is not recommended for the treatment of P. vivax malaria by the World Health Organization and the Malaria National Programs.     

错配杂交化学发光法检测亚甲基四氢叶酸还原酶基因多态性

目的 建立一种基于错配杂交及化学发光技术的检测亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reducatase,MTHFR）基因多态性的新方法。方法 针对多态位点设计两条寡核苷酸探针,分别与野生型及突变型序列互补。将两条探针分别与含多态位点C677T的PCR扩增产物杂交,然后用化学发光法检测,根据两条探针的发光值之比确定样品的基因型。结果 用本法随机检测了50例DNA样品,结果3种基因型的发光值之比可以严格区分,其中野生型（C／C）15例,杂合型（C／T）28例,突变型（T／T）7例,与参考方法（PCR—RFLP）的检测结果完全一致。结论 本方法操作简便、检测快速而且费用低廉,可广泛应用于MTHFR基因突变及多态性检测。     

血浆同型半胱氨酸及亚甲基四氢叶酸还原酶基因多态性与缺血性脑卒中的相关性研究

目的探讨血浆同型半胱氨酸(Hcy)及亚甲基四氢叶酸还原酶(MTHFR)基因多态性与缺血性脑卒中的相关性。方法急性缺血性脑卒中患者148例为缺血性脑卒中组,同时健康体检者100例为对照组。患者入院后行血压、血糖、血脂等常规检查。清晨空腹取肘静脉血5 mL,EDTA抗凝后离心10 min,分离上层血浆,检测Hcy水平;中层白细胞4℃保存,3 d内行基因组DNA提取。结果缺血性脑卒中组患者血浆Hcy水平为(15.9±1.9)μmol/L,对照组血浆Hcy水平为(12.0±1.1)μmol/L,2组比较有显著差异。缺血性脑卒中组的高Hcy血症患者比率为39.3%,明显高于对照组中高Hcy血症患者比率(19.0%)。2组T/T纯合子组的血浆Hcy水平均明显高于非T/T纯合子组。结论缺血性脑卒中与高Hcy血症相关,MTH-FR基因对血浆Hcy水平影响显著。     

Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folate-deficient population

Background: A large body of evidence links plasma concentrations of homocysteine and cardiovascular disease. Several genetic and environmental variables may modulate such relationship. We investigated the influence of methylenetetrahydrofolate reductase (MTHFR) gene variants C677T, A1298C, and T1317C on homocysteine, folate, and cobalamin concentrations in a sample of individuals from a mild folate deficiency population to better clarify the complex interactions existing among these variables. Methods: In the present study, 209 individuals belonging to an admixed urban population characterized by mild folate deficiency were investigated. MTHFR gene variants C677T, A1298C, and T1317C were genotyped and homocysteine-, folate-, and cobalamin-determined for each individual. Results: Univariate analyses showed a significant association between the C677T variant with homocysteine (P<0.001) and cobalamin (P=0.005) as well as a significant relationship between the T allele and serum folate concentrations (P<0.05). The TT genotype of the C677T polymorphism remained significantly associated with log-transformed homocysteine even after adjustment for age, sex, smoking status, ethnicity, folate, and cobalamin concentrations (P<0.01). Both univariate and multivariate analysis have failed to show any effect of the A1298C and T1317C genetic variants in homocysteine concentrations in this population. Finally, a significant interaction between folate and C677T polymorphism in the determination of homocysteine was also disclosed (P<0.005). Conclusions: Taken together, these results demonstrate a significant interaction between serum folate and MTHFR genotype in predicting homocysteine concentrations. One may consider that a differential response of homocysteine to folic acid supplementation may depend on MTHFR genotype which may have important implications when attempting to lower homocysteine concentrations in populations with mild folate deficiency.     

Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes

OBJECTIVE: We screened the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic subjects and investigated whether the previously reported and novel polymorphisms were associated with neurophysiologic deterioration and clinical peripheral neuropathy. RESEARCH DESIGN AND METHODS: The study population included 85 Finnish type 2 diabetic and 126 nondiabetic subjects. The genetic analyses were performed using the PCR, single-strand conformation polymorphism, restriction fragment-length polymorphism, and automated laser fluorescence scanning analyses. A detailed neurologic examination and neurophysiologic analyses were performed at the time of diagnosis and at the 10-year examination. RESULTS: The genetic screening identified four polymorphisms: C-106T, C-11G, A11370G, and C19739A. The C and Z-2 alleles of the C-106T polymorphism and the previously reported (CA)(n) repeat marker were more frequent in type 2 diabetic subjects than in nondiabetic subjects. At baseline, the diabetic subjects with the T allele of the C-106T polymorphism had lower sensory response amplitude values in the peroneal (P = 0.025), sural (P = 0.007), and radial (P = 0.057) nerves and, during follow-up, a greater decrease in the conduction velocity of the motor peroneal nerve than those with the C-106C genotype. No associations were found between the polymorphisms examined and clinical polyneuropathy. CONCLUSIONS: The C-106T polymorphism of the ALR gene may contribute to an early development of neurophysiologic deterioration in type 2 diabetic patients.     

Selection of Drug Resistance-Mediating Plasmodium falciparum Genetic Polymorphisms by Seasonal Malaria Chemoprevention in Burkina Faso

Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs in P. falciparum isolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment in P. falciparum PCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P = 0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00941785","term_id":"NCT00941785"}}NCT00941785.)     

Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wall

BACKGROUND: The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. MATERIALS AND METHODS: The autopsy study included 123 subjects (90 males and 33 females) aged 18-93. For the light microscopy, a 0.5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. RESULTS: The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2.02 +/- 2.25 vs. 2.53 +/- 1.89, P < 0.04 and 0.56 +/- 1.09 vs. 1.82 +/- 2.66, P < 0.02, respectively). The trend was similar for the coeliac and the right renal arteries. CONCLUSIONS: Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL.     

中国西北地区人群高同型半胱氨酸血症、亚甲基四氢叶酸还原酶多态性与缺血性脑卒中的关系

背景血浆中总同型半胱氨酸水平增高是缺血性脑卒中的一项危险因素,5,10-亚甲基四氢叶酸还原酶是同型半胱氨酸代谢途径中的关键酶.关于5,10-亚甲基四氢叶酸还原酶与缺血性脑卒中的关系还存在争议.目的通过检测中国西北地区汉族人群中缺血性脑卒中患者血浆中总同型半胱氨酸水平和5,10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型,探讨三者之间的关联性.设计病例-对照实验.单位吉林大学第一附属医院神经内科,解放军第四军医大学西京医院神经内科.对象病例组随机选取2001-11/2002-05解放军第四军医大学西京医院神经内科经CT或磁共振确诊的缺血性脑卒中患者97例,男71例,女26例.对照组94例,无脑卒中病史,其中男58例,女36例.以上两组受试者有脑出血,癌症,肾功能障碍及服用维生素和雌激素的排除在外.方法血浆总同型半胱氨酸水平用全自动荧光偏振免疫分析法检测,5,10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型用聚合酶链式反应-限制性片段多态性分析法检测.主要观察指标脑卒中患者C677T和A1298C的基因型频率,血浆总同型半胱氨酸水平.结果677T等位基因在病例组的分布明显高于对照组(59.3%,44.7%,P=0.006),但是1298C等位基因的频率在两组间较接近(22.7%,19.7%,P＞0.05).677TT纯合子与高同型半胱氨酸血症显著相关(P＜0.01).Logistic分析表明,C677T突变及高同型半胱氨酸血症者患缺血性脑卒中的OR值分别是1.87和1.03(P＜0.05).结论高同型半胱氨酸血症是缺血性脑卒中的危险因素.C677T基因突变与缺血性脑卒中的发生相关,显著影响血浆总同型半胱氨酸水平,可能是缺血性脑卒中的一个独立的遗传危险因素.