L-精氨酸对原发性高血压影响的临床研究

目的:从血流动力学及神经内分泌学两方面探讨左旋精氨酸(L-Arg)-一氧化氮(NO)通路对原发性高血压的影响。方法: 选择24例高血压病人随机分为两组,一组静滴L-Arg ,一组静滴生理盐水,观察其血压、心率及心功能,同时检测血浆中NO、血管紧张素Ⅱ(AngⅡ)、内皮素(ET)、血栓素A₂(TXA₂)以及前列环素(PGI₂)以探讨其降压机理。 结果:L-Arg治疗后,病人血压下降、心率增快,心输出量(CO)、每搏输出量(SV)、射血分数(EF)增加,总外周阻力(TPR)降低,血浆NO、PGI₂含量升高,ET、AngⅡ、TXA₂水平降低。静滴80 min时,随NO浓度降低CO、SV、EF也随之降低,而TPR又回升,血浆ET、AngⅡ发生相应变化,TXA₂、PGI₂无明显改变。结论:L-Arg通过直接升高血浆NO水平引起血流动力学改变,通过间接反馈效应改变ET、AngⅡ水平,并可抑制血小板聚集。     

MTHFR基因C677T多态性与冠心病患者血浆同型半胱氨酸和叶酸水平相关

目的研究宁夏地区汉族人群5,10-亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态性、同型半胱氨酸水平(Hcy)及叶酸水平与冠心病(CHD)的相关性。方法用病例-对照研究方法、应用限制性片段长度多态性扩增技术(PCR-RFLP)分析宁夏地区汉族202例冠心病患者及199例正常人群MTHFRC677T基因型频率及基因频率的分布特点。荧光偏振免疫分析法测定血浆Hcy水平,化学发光免疫分析法测定血清叶酸、VitB12浓度。结果 (1)病例组与对照组MTHFRC677T基因型频率分别为CC型23.3%vs20.7%、CT型52.3%vs54.5%和TT型24.4%vs24.8%,两组间基因型及等位基因频率分布无差异。(2)冠心病患者组中MTHFR基因C677TCC基因型患者血浆Hcy浓度(10.84μmol/L)较T基因携带者(12.24μmol/L)低(P<0.01)。CC基因型患者血浆叶酸浓度(5.38μg/L)较T基因携带者(3.72μg/L)高(P<0.05)。结论 MTHFRC677T的3种基因型频率在宁夏汉族冠心病患者和正常人群中的分布无统计学意义。MTHFR基因C677T多态性与冠心病的危险因素Hc...     

叶酸代谢相关基因多态性及血浆同型半胱氨酸与唐氏综合征关系研究

目的研究叶酸代谢相关的亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTH-FR)基因多态性与唐氏综合征(Down syndrome,DS)发生的关系。方法选择100例生育过DS患儿的汉族母亲及100名相匹配的正常对照组母亲,PCR-限制性片段长度多态性方法检测MTHFR677C/T的基因型,化学发光法检测血浆中同型半胱氨酸(homocysteine,HCY)的水平。结果病例组MTHFR677T等位基因的频率较对照组增高,差异有统计学意义(P=0.002);杂合基因型CT的比值比为2.12(95%CI:1.14～3.94);而纯合基因型TT的比值比为3.43(95%CI:1.41～8.36)。平均血浆HCY浓度在病例组[(9.04±3.85)μmol/L]较对照组[(6.53±2.06)μmol/L]增高,差异有统计学意义(P<0.01)。MTHFR677位点一个和(或)两个等位基因C→T的变异,不论在病例组还是对照组均可引起HCY水平的显著增加(P<0.01)。同为MTHFR677CC基因型,病例组中的血浆HCY浓度仍较对照组增高(P<0.01),这种增加不依赖于MTHFR的基因型。结论血浆HCY和叶酸代谢相关基因的遗传多态性是汉族妇女生育DS患儿的危险因素。     

亚甲基四氢叶酸还原酶基因677C→T突变与糖尿病微血管病

目的 研究中国人群2型糖尿病患者中,亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR)基因677C→T突变与糖尿病微血管病的关系。方法 将168名研究对象分为正常对照组、糖尿病和糖尿病微血管病（diabetic microangiopathy,DMA)组,采用PCR－RFLP检测各组MTHFR677C→T突变,统计各组对象的突变频率。结果 与无糖尿病微血管病患者和正常人相比,糖尿病微血管病患者MTHFR677C→T（T／T基因型）变频率更高（22．6％vs6.7%和5．5％,P＜0．01）,MTHFRT／T基因型对MDA的OR值为3．36,P＜0．001。结论 糖尿病患者中MTHFR677C→T突变为其发生微血管病的一种遗传易感因素。     

血浆Hcy水平及MTHFR和MTRR基因多态性与复发性流产的相关性研究

目的探讨血清同型半胱氨酸(Hcy)水平及亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与不明原因复发性流产的相关性。方法以84例复发性自然流产的患者作为病例组,60例已有1次正常生育史,且既往无不良孕产史的妇女作为对照组,应用荧光定量PCR技术检测MTHFR基因C677T、A1298C和MTRR A66G位点的多态性,同时应用比色法检测血清Hcy水平。比较病例组和对照组间各种基因型和血清Hcy水平的差异。结果病例组血清Hcy水平明显高于对照组;高Hcy是先兆流产的危险因素(OR=2.132,P=0.021);MTHFR C677位点TT基因型携带者血清Hcy水平明显高于其他基因型;A1298位点CC基因型携带者血清Hcy水平明显高于AA野生型;MTRR A66位点GG基因型携带者血清Hcy水平明显高于其他基因型,差异均有统计学意义(P0.05)。结论 Hcy升高是导致复发性流产的重要危险因素;MTHFR基因C677T、A1298C和MTRR A66G位点的多态性改变均可致血清Hcy水平升高,与复发性流产的发生有一定的相关性。     

血管紧张素Ⅱ对心房颤动患者外向钾电流的作用

目的：研究血管紧张素Ⅱ(AngⅡ)对心房颤动(AF)患者心房肌外向钾电流的作用及其受体机制。方法: 采用急性酶解法获取游离心房肌细胞，应用膜片钳全细胞技术记录外向钾电流。结果: (1) 在钳制电位-10 mV~+50 mV时, AF组瞬时外向钾电流(I_to1)密度明显低于窦性心律(SR)组（P<0.01），而持续性外向钾电流（I_sus）密度与SR组无明显差异。(2) 以0.1 μmol/L AngⅡ灌流后，在钳制电位0 mV~+50 mV时，SR患者的Ito1密度明显低于灌流前（P<0.01），其动力学特性没有改变，AngⅡ对AF组I_to1的抑制作用明显低于SR组 (P<0.01)。0.1 μmol/L AngⅡ对两组I_sus没有影响。(3) AngⅡ对Ito1的抑制作用可逆，10 μmol/L缬沙坦（valsartan）以及1 μmol/L沙拉新(saralasin)均能完全消除0.1 μmol/L AngⅡ对Ito1的抑制，以10 μmol/L valsartan灌流后，膜电位+50 mV时I_to1的电流密度增加（22.46±4.30）%。结论: AngⅡ通过Ⅰ型受体（AT₁R）介导，明显抑制心房肌细胞膜I_to1，是AF患者心房肌瞬时外向钾通道电重构的机制之一。     

河源地区汉族女性MTHFR基因多态性调查及其与血清HCY水平相关性的研究

目的调查广东省河源地区汉族女性5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C位点基因多态性分布特征,研究分析遗传因素与血清同型半胱氨酸(HCY)的相关性,为本地区育龄妇女个性化补服叶酸及出生缺陷的一级预防提供依据。方法以该地区1423位汉族女性为研究对象,检测其MTHFR C677T、A1298C基因位点多态性,与我国其他南北各地区既有数据对比,采用统计学方法分析基因的多态性分布特征;对其中418位孕期女性测定血清同型半胱氨酸浓度,分析该生化指标与遗传因素的相关性。结果本地区的汉族女性MTHFR 677TT基因型频率(7.4%),MTHFR 1298CC基因型频率(5.6%)。C677T和A1298C位点三种基因型间血清HCY水平差异无统计学意义(P0.05)。结论本地区汉族女性MTHFR基因C677T、A1298C位点多态性分布特征有其自身的特点;基因位点的多态性变化对血清同型半胱氨酸水平无显著性影响。     

MTHFR C677 T基因多态性及血浆HCY与复发性流产的关系

目的探讨亚甲基四氢叶酸还原酶基因多态性(MTHFR C677T)及血浆同型半胱氨酸(HCY)与复发性流产的关系。方法非孕期复发性流产患者100例,对照组50例,MTHFR基因C677T多态性采用聚合酶链反应-限制性片段长度多态性技术检测,HCY检测采用酶循环法于全自动生化分析仪上完成。结果病例组的HCY水平明显高于对照组,差异有统计学意义(P0.05);对两组进行MTHFR基因型及频率分析,病例组TT基因型虽较对照组高,但差异无统计学意义(P0.05);组别和基因型间的HCY水平的比较,得出组别和基因型之间HCY水平差异均具有统计学意义(P0.05)。不同基因型进行组内两两比较,得出TT与CT、CC均具有统计学差异,CT、CC之间没有统计学差异。结论患者MTHFR C677T突变及血浆HCY水平的增高与复发性流产关系密切。     

MTHFR C677T多态性与脓毒血症的关系

目的 探讨MTHFR C677T基因多态性（SNP）与脓毒血症的关系。方法 选择2014年1月~2018年6月我院住院的脓毒血症患者98例,采用梯度PCR及DNA测序技术,检测MTHFR C677T基因型,比较不同T淋巴细胞凋亡比例脓毒血症患者MTHFR C677T基因型分布情况及MTHFR C677T多态性与脓毒血症的关系。结果 MTHFR C677各位点基因型在T淋巴细胞中的凋亡比例方面比较,差异均无统计学意义（P＞0.05）;APACHEⅡ＜4分,SOFA＜2分的CT比例高于CC与TT基因型,降钙素原减少比例TT低于CC基因型与CT基因型,差异均有统计学意义（P＜0.05）,28 天死亡人数比例TT低于CC基因型与CT基因型,差异均有统计学意义（P＜0.05）。结论 MTHFR C677T与脓毒血症患者预后有关,可根据MTHFR C677T的基因多态性预测脓毒血症的预后。     

MTHFR基因多态性与血浆同型半胱氨酸在妊娠期高血压疾病的相关性研究

目的 探讨四氢叶酸还原酶（MTHFR）C677T基因多态性及血浆同型半胱氨酸（Hcy）在妊娠期高血压疾病（HDP）发病机制中的作用。方法 用过枉法提取基因型DNA，并行聚合酶链反应物-直接测序法检测和分析MTHFR基因中C677T的分型，用微粒酶免疫发光法测量血浆同型半胱氨酸水平。结果 ①HDP组与对照组C677／T677比较差异有统计学意义（P〈0．05），HDP组T677等位基因频率（0．488）显著高于对照组（0．325），两组比较差异有统计学意义（P〈0．01）。②轻度子痫前期组、重度子痫前期组的血浆Hcy水平均高于对照组，分别比较，差异均有统计学差异（P〈0．001）。结论 ①妊娠期高血压疾病患者的MTHFR C677T基因多态性可能是妊娠期高血压疾病发生的诱因之一，T667等位基因可能是妊娠高血压疾病的易感基因。②血浆Hcy水平升高可能是子痫前期发病的危险因素。     

Amniotic fluid homocysteine levels, 5,10‐methylenetetrahydrafolate reductase genotypes,and neural tube closure sites

A specific gene mutation leading to altered homocysteine metabolism has been identified in parents and fetuses with neural tube defects (NTDs). In addition, current animal and human data indicate that spine closure occurs simultaneously in five separate sites that then fuse. We sought to determine whether either this mutation or abnormal amniotic fluid homocysteine levels are associated with all five neural tube closure sites. We retrieved stored amniotic fluid from cases of isolated fetal neural tube defect diagnosed from 1988 to 1998 (n = 80) and from normal controls matched for race, month and year of amniocentesis, and maternal age. Cases were categorized according to defect site by using all available medical records. The presence or absence of the 677C→T mutation of 5,10‐methylenetetrahydrafolate reductase (MTHFR) gene was determined, and homocysteine levels were measured; case and controls were compared. Significantly more cases than controls were heterozygous or homozygous for the 677C→T MTHFR mutation (44% vs. 17%, P ≤ 0.001). Likewise, cases were significantly more likely than controls to have amniotic fluid homocysteine levels >90th centile (>1.85 μmol/L), 27% vs. 10%, P = 0.02. Most (83%) of control cases had both normal MTHFR alleles and normal amniotic fluid homocysteine levels (normal/normal), whereas only 56% of NTD case were normal/normal (P = 0.001). When evaluated by defect site, only defects involving the cervical‐lumbar spine, lumbosacral spine, and occipital encephalocele were significantly less likely to be normal/normal than controls (P = 0.007, 0.0003, and 0.007, respectively), suggesting a strong association with the 677C→T allele. In contrast, anencephaly, exencephaly, and defects confined to the sacrum included many cases that had both normal MTHFR alleles and normal homocysteine and were not significantly different from controls. The 677C→T MTHFR mutation and elevated homocysteine levels appear to be disproportionately associated with defects spanning the cervical‐lumbar spine, lumbosacral spine, and occipital encephalocele. In contrast, anencephaly, exencephaly, and defects confined to the sacrum may not be related to altered homocysteine metabolism. Am. J. Med. Genet. 90:6–11, 2000. © 2000 Wiley‐Liss, Inc.     

Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.

A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR activity and associated with modestly increased plasma homocysteine concentrations. Since underlying maternal vascular disease increases the risk of pre-eclampsia, we had the working hypothesis that pre-eclampsia patients would have an increased T677 allele frequency compared with controls. The MTHFR genotypes were determined in 67 pre-eclampsia patients, 98 normal pregnant women, and 260 healthy adults by the PCR/RFLP method. The T677 allele and the genotype homozygous for the T677 allele were significantly increased in the pre-eclamptic group compared with the controls (p < 0.02 and p < 0.004, respectively). The data indicate that the T677 variant of the MTHFR gene is one of the genetic risk factors for pre-eclampsia.     

同型半胱氨酸代谢酶基因多态性与深静脉血栓的相关性研究

目的探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因C677T、甲硫氨酸合成酶（methionine synthase，MS）基因A2756G和胱硫醚β-合成酶（cystathionine β-synthase，CBS）基因844ins68这3种基因突变在深静脉血栓发病中的意义。方法应用聚合酶链反应-限制性片段长度多态性方法对103例深静脉血栓患者和250名健康对照者进行MTHFR C677T、MS A2756G和CBS 844ins68基因多态性的分析，并进行基因型及等位基因频率的计数。对MTHFR C677T和MS A2756G两位点进行单倍型分析。结果MTHFR C677T TT基因型在深静脉血栓组的分布频率（27．2％）高于对照组（17．2％），经χ^2检验差异有统计学意义（P〈0．05）。MS A2756G AG基因型在深静脉血栓组的分布频率（9．7％）低于对照组（19．2％），经χ^2检验差异有统计学意义（P〈0．05）。单倍型分析显示病例组中677T-2756A单倍型频率明显高于对照组（P〈0．05），677C-2756A单倍型频率明显低于对照组（P〈0．05）。CBS 844ins68基因型在两组的分布频率差异无统计学意义。结论MTHFR C677T多态性中TT基因型可能是深静脉血栓形成的一个遗传风险因子，MS 2756 AG基因型可能会减少深静脉血栓的发生。677T-2756A单倍型可能是静脉血栓的危险因素，677C-2756A单倍型可能是静脉血栓的保护因素。CBS 844ins68基因突变可能存在种族或地域的差异。     

Role of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase in ischemic stroke.

A common mutation in methylenetetrahydrofolate reductase (MTHFR), a homocysteine metabolic pathway enzyme, has been associated with increased homocysteine levels and increased risk for premature cardiovascular disease. The purpose of this study was to assess the association between the prevalence of the MTHFR mutation, hyperhomocysteinemia, and subtypes of ischemic stroke in an elderly population comprised of three age-balanced groups of patients. The presence of the C677T MTHFR mutation was determined by a direct polymerase chain reaction-based assay performed on blood samples from 136 patients with acute ischemic stroke, 95 patients with atherosclerotic risk factors for stroke (including some with a history of previous stroke or transient ischemic attack), and 52 healthy control subjects. The prevalence of the homozygous C677T mutation was not significantly higher in the elderly stroke patients (7%) than in the atherosclerotic risk (8%) or healthy elderly control (2%) groups. Plasma homocysteine levels were higher in the acute stroke patient group (14.5+/-4.5 micromol/L) and atherosclerotic risk patient group (14.6+/-6.2 micromol/L) compared with the control subjects (10.3+/-3.1 micromol/ L, P < 0.03). Homozygotes for the C677T MTHFR mutation did not have significantly higher homocysteine levels than non-homozygotes. Moderate hyperhomocysteinemia, though common in older patients with ischemic cerebrovascular disease, is not attributable, at least in this patient group, to a higher prevalence of the C677T MTHFR mutation.     

The C677T mutation in the methylene tetrahydrofolate reductase gene increases serum uric acid in elderly men

A common mutation, C677T, in the methylene tetrahydrofolate reductase gene (MTHFR) reduces the activity of MTHFR and increases total homocysteine levels in plasma. Increased homocysteine levels are reportedly associated with high serum uric acid levels. The relationship between the MTHFR mutation and uric acid metabolism remains unclear, however. To investigate whether the C677T MTHFR mutation is a risk factor for hyperuricemia, we performed MTHFR genotyping and clinical laboratory determinations, including serum uric acid, in 271 elderly Japanese men (age range, 40–79 years; mean, 52.6 years). The mean uric acid levels for the C/C, C/T, and T/T genotypes were 5.67, 6.00, and 6.39 mg/dl, respectively (P = 0.012). The T/T genotype was more frequent in subjects with high uric acid levels than in those with low uric acid levels (P = 0.038). These findings suggest that the C677T MTHFR mutation contributed to higher uric acid levels in subjects enrolled in this study. In conclusion, the mutation of the MTHFR gene may be a risk factor for hyperuricemia in elderly men. Received: February 28, 2000 / Accepted: February 29, 2000     

Methylenetetrahydrofolate reductase and spina bifida: evaluation of level of defect and maternal genotypic risk in Hispanics

The C677T and A1298C mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are each associated with reduced MTHFR activity. The C677T mutation in the heterozygous and homozygous state correlates with increased enzyme thermolability, with homozygous mutant genotypes showing significantly elevated plasma homocysteine levels and decreased plasma folate levels. The A1298C mutation results in decreased MTHFR activity, but changes in neither homocysteine nor folate levels are associated with A1298C variant genotypes. Our study determined the frequencies of the C677T and A1298C MTHFR mutations for spina bifida (SB) cases, mothers and fathers of SB cases, and controls in Hispanics of Mexican-American descent. In addition, our subject population was further categorized as to whether the spina bifida lesion occurred as an upper or lower level defect, according to the Van Allen "multi-site closure" model. Hispanic SB cases with upper level defects and their mothers were homozygous for the C677T variant allele at a higher rate than their respective controls (OR = 1.5 [95% CI 0.8-2.9], P = 0.30; OR = 2.3 [1.1-4.8], P = 0.04, respectively), with statistically significant results seen only for the maternal homozygous genotype. Homozygosity for the A1298C mutation was seen at a higher rate only in Hispanic mothers of both upper and lower level SB cases when compared to controls, but these results were not statistically significant. Our study provides evidence that the maternal C677T MTHFR homozygous mutant genotype is a risk factor for upper level spina bifida defects in Hispanics.     

Methylenetetrahydrofolate reductase polymorphism (c677t) in muslim population of eastern uttar pradesh, India

Objective : The aim of the present study was to investigate the distribution of methylenetetrahydrofolate reductase (C677T) polymorphism in the Muslim population of eastern Uttar Pradesh. Materials and Methods: Total 56 subjects were analysed for MTHFR C677T polymorphism. C677T mutation analysis was done according to the PCR-RFLP (Polymerase chain reaction-Restriction fragment length polymorphism) method. Results : The frequencies of three genotypes CC, CT, and TT were 0.857, 0.125, and 0.07, respectively, and the frequency of mutated T allele was found to be 0.080. Conclusion : Genotypes and allele frequencies revealed the low prevalence of MTHFR C677T polymorphism in Indian Muslims. C677T mutation has been suggested to be positively associated with the risk of several congenital and multifactorial disorders. The low frequency of T/T genotype in the Muslim population may be due to malnutrition in pregnant women, because of insufficient intake of folate is considered to be a survival disadvantage for foetuses with T/T genotype.     

Role of amniotic fluid homocysteine level and of fetal 5,10‐methylenetetrahydrafolate reductase genotype in the etiology of neural tube defects

A mutation in the gene 5,10‐methylenetetrahydrofolate reductase (MTHFR), leading to altered homocysteine metabolism, has been identified in parents and fetuses with fetal neural tube defects. We sought to determine which is of greater importance in fetal neural tube defect formation: the fetal MTHFR mutation or elevated amniotic fluid homocysteine level. We retrieved stored amniotic fluid from cases of isolated fetal neural tube defect diagnosed from 1988 to 1998 (n = 80), and from normal controls matched for race, month and year of amniocentesis, and maternal age. The presence or absence of the 677C→T mutation of MTHFR was determined and homocysteine levels were measured; cases and controls were compared. Significantly more cases than controls were heterozygous or homozygous for the 677C→T MTHFR mutation (44% vs 17%, P ≤ 0.001). Cases were also significantly more likely than controls to have an amniotic fluid homocysteine level above the 90th centile (>1.85 μmol per liter); 27% vs 10%, P = 0.02. Thirty one cases and 12 controls had an abnormal genotype; however, amniotic fluid homocysteine levels were not significantly different between these two groups (6/31, or 19% of cases had an elevated homocysteine compared to 1/12, or 8% of controls; P = 0.65). In contrast, 40 cases and 60 controls had a normal genotype; the neural tube defect cases had significantly higher homocysteine levels (13/40, or 32% of cases had an elevated homocysteine level compared to only 6/60, or 10% of controls; P = 0.008). Although both abnormal fetal MTHFR genotype and abnormal amniotic fluid homocysteine concentration are significantly associated with neural tube defects, the association with amniotic fluid homocysteine concentration is significant regardless of the fetal MTHFR genotype. The relationship between maternal and fetal homocysteine metabolism is complex. Am. J. Med. Genet. 90:12–16, 2000. © 2000 Wiley‐Liss, Inc.     

MTHFR基因C677T多态性与Down综合征发生的相关研究

目的研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与Down综合征关系。方法采用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)法对32例DS患儿母亲,70例未生育DS患儿女性MTHFR的C677T进行基因分析。比较上述各组基因型和等位基因频率分布有无差异。结果MTHFR基因C677T突变型等位基因(T)频率在实验组和对照组中有显著性差异,CC、TT基因型频率分布差异有显著性(P<0.05)。CT基因型比CC基因型生育DS患儿风险高2.84倍,TT基因型比CC基因型生育DS患儿风险高9.26倍。结论MTHFRC677T基因多态性与Down综合征发生相关,TT基因型增加了Down综合征的发生风险,CC基因型是降低Down综合征发生的保护性因素。     

甲基四氢叶酸还原酶基因多态性与糖尿病肾病关系的研究

目的：探讨甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR)基因多态性与糖尿病肾病（diabetic nephropathy,DN)发生的关系。方法：利用聚合酶链反应－限制性片段长度多态性分析法（PCR－RFLP）检测了85名健康人和经尿微量白蛋白检测确诊的82例合并DN和79例无DN的2型糖尿病患者MTHFR基因第677位碱基多态性。结果：DN患者MTHFR基因变异型纯合子和等位基因频率均明显高于无肾病患者及健康者,P＜0．01。结论：MTHFR基因第677位碱基变异可能是中国汉族人DN发生的一个遗传危险因子。