亚甲基四氢叶酸还原酶基因多态性与糖尿病微血管并发症相关性研究

目的：探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与中国人2型糖尿病微血管并发症的关系。方法：运用PCR—RFLP检测263例中国人(206例为2型糖尿病，其中148例合并肾病或视网膜病变，57例为正常对照组)MTHFR基因C677T位碱其突变，比较各组间等位基因频率和基因型频率。结果：(1)同时合并肾病和视网膜病变的2型糖尿病组与无微血管并发症的2型糖尿病组及正常对照组相比，TT基因型频率显著增加，突变等位基因T频率也明显升高。(2)2型糖尿病合并肾病组TT基因型频率及T等位基因频率明显高于不伴有肾病的2型糖尿病组及正常对照组。(3)2型糖尿病合并视网膜病组与无视网膜病的2型糖尿病及正常对照组相比，TT基因型频率及T等位基因频率明显升高。结论：MTHFR基因C677T碱基突变是促进中国人2型糖尿病患者并发微血管并发症的危险因子，突变T等位基因是糖尿病微血管并发症的易感基因。     

亚甲基四氢叶酸还原酶基因多态性与糖尿病肾病相关性研究

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病的关系。方法：运用聚合酶链反应－限制性片段长度多态性技术（PCR－RFLP）检测85例2型糖尿病患者（其中39例伴糖尿病肾病）及57例正常对照组MTHFR C677T基因型,采用高效液相色谱法测定血浆同型半胱酸水平。结果：糖尿病肾病组MTHFR基因TT纯合基因型,CT杂合基因型及T等位基因频率（分别为38．21％,51．28％,53．85％）均明显高于糖尿病不伴肾病组（分别为19．57％,28．26％,33．70％）及正常对照组（分别为17．54％,28．07％,31．58）,基因型和等位基因频率分布差异均有统计学意义（P＜0．05）,而MTHFR基因该多态性在不伴肾病组与正常对照组之间差异无显著性（P＞0．05）,T等位基因与糖尿病肾病的发生密切相关（OR＝2．30,95％可信区间;1．24－4．26）。糖尿病肾病组,糖尿病不伴肾病组及正常对照组中,MTHFR基因有C677T突变者血浆同型半胱氨酸水平均显著高于无基因突变者。结论：MTHFR基因C677T位碱基突变致血浆同型半胱氨酸水平高是糖尿病肾病发病的重要遗传因素。     

2型糖尿病肾病亚甲基四氢叶酸还原酶基因多态性研究

目的探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate     

No association between MTHFR gene polymorphism and diabetic nephropathy in Japanese type II diabetic patients with proliferative diabetic retinopathy

The development of diabetic nephropathy shows marked variation among individuals. Not only hyperglycemia, but also genetic factors may contribute to the development of diabetic nephropathy. Methylenetetrahydrofolate reductase (MTHFR) is involved in remethylation of homocysteine to methionine. Decreased activity of MTHFR which can result in hyperhomocysteinemia may lead to cerebrovascular disease and coronary artery disease. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C>T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. In the present study, we recruited 173 of Japanese type II diabetic patients with proliferative diabetic retinopathy who would be exposed to long-term hyperglycemia, and examined the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy as microangiopathy. The frequency of the mutated allele was 43.3% in patients with nephropathy (n = 105) versus 41.9% in those without nephropathy (n = 68). The genotype frequencies were +/+, 16.2%; +/−, 54.3%; −/−, 29.5% in patients with nephropathy versus +/+, 13.2%; +/−, 57.4%; −/−, 29.4% in those without nephropathy (+ indicates the presence of the mutation). The MTHFR genotype and allele frequencies were not significantly different between patients with and without nephropathy. Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Japanese type II diabetic patients.     

Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese type 2 diabetic patients

OBJECTIVE: Genetic predisposition has been implicated in diabetic nephropathy (DN). The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, may play a role in the development of not only vascular disease but also diabetic microangiopathies. In this study, we examined the distribution of the MTHFR genotypes in the Chinese population and the association between the C677T variant and diabetic nephropathy. METHODS: 220 unrelated patients with type 2 diabetes mellitus and 130 controls were recruited. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS: In 130 healthy control subjects, the frequency of the mutant T allele was 30.0%, comparable to that of a Hong Kong (Chinese) population. The distribution of the three genotypes was as follows: TT genotype, 16.9%; CT genotype, 26.2%; and CC genotype, 56.9%. This genotype distribution did not differ between control subjects and type 2 diabetic patients in which 19.1% were TT, 34.5% were CT and 46.4% were CC (2=3.85, P>0.05). The frequency of the mutant T allele was 42.3% in diabetic patients with nephropathy (n=124) versus 28.6% in those without nephropathy (n=96). The genotype frequencies were TT, 21.0%; CT, 42.7%; CC, 36.3% in diabetic patients with nephropathy versus TT, 16.7%; CT, 23.9%; CC, 59.4% in those without nephropathy. The MTHFR genotype and allele frequencies were different between diabetic patients with and without nephropathy (chi2=12.27, P<0.005; chi2=8.77, P<0.005, respectively). Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotype. CONCLUSIONS: The C677T mutation of MTHFR gene is common in the Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels may represent a genetic risk factor for diabetic nephropathy in Chinese type 2 diabetic patients.     

The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy

BACKGROUND: Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy. METHODS: DNA was extracted from peripheral leukocytes of the subjects. Genotyping of the MTHFR C677T polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR. RESULTS: This genotype distribution did not differ between control subjects and type 2 diabetic patients in which 6.8% were TT, 43.7% were CT and 49.5% were CC (chi2 = 0.201, p > 0.05). The frequency of the mutant T allele was 23.4% in diabetic patients with nephropathy versus 33.0% in those without nephropathy. The genotype frequencies were TT, 2.1%; CT, 46.6%; CC, 55.3% in diabetic patients with nephropathy versus TT, 10.7%; CT, 44.6%; CC, 44.6% in those without nephropathy. CONCLUSIONS: The MTHFR genotype and allele frequencies were not different between diabetic patients with and without nephropathy (chi2 = 3, 386, p > 0.005; chi2 = 2.320, p > 0.005, respectively). Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients.     

MTHFR gene polymorphism is susceptible to diabetic retinopathy but not to diabetic nephropathy in Japanese type 2 diabetic patients

AIMS: Previously, we have proposed that methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T) could be a risk factor for diabetic retinopathy. To support our suggestion, we examined in detail the association of MTHFR polymorphism with diabetic retinopathy and nephropathy in Japanese type 2 diabetic patients. METHODS: Subjects (n=190) were free of cardiovascular diseases and were not on hemodialysis. Retinopathy was assessed according to fundamental differentiation; nephropathy was determined according to urinary albumin level; and MTHFR genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. We also analyzed how hyperglycemia affected these three conditions in 131 patients with glycosylated hemoglobin > or =6.5% and fasting blood sugar > or =110 mg/dl. RESULTS: The frequency of 677T/677T homozygous subjects with retinopathy was higher than the frequencies of the other two genotypes, and a significant difference was observed in the distribution of the genotypes (677C/677C, 41.9%; 677C/677T, 31.1%; 677T/677T, 61.5%; P<.05). The susceptibility of 677T/677T homozygote to retinopathy approached significance [odds ratio (OR)=2.17; 95% confidence interval (95% CI)=0.87-5.42]. However, in the population with hyperglycemia, the 677T/677T homozygote modified the risk for retinopathy (OR=4.30; 95% CI=1.42-13.1), especially the risk for nonproliferative retinopathy. In contrast, the 677T/677T homozygote did not affect the risk for nephropathy (OR=1.17; 95% CI=0.45-3.05), even in subjects with hyperglycemia (OR=1.50; 95% CI=0.50-4.48). CONCLUSIONS: Our results are highly suggestive of an important role for MTHFR genotype in susceptibility to retinopathy under hyperglycemia, but not to nephropathy. Preventive therapies based on MTHFR polymorphism could delay the onset of retinopathy in type 2 diabetic patients.     

Methylenetetrahydrofolate reductase polymorphism associated with susceptibility to coronary heart disease in Chinese type 2 diabetic patients

OBJECTIVE: Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for atherosclerosis. The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, might play a role in the development of coronary heart disease (CHD). In this study, we examined the distribution of the MTHFR genotypes in the Chinese population and the association between the C677T variant and CHD in Chinese type 2 diabetic patients. METHODS: Two hundred and twenty-eight unrelated patients with type 2 diabetes mellitus (126 with coronary heart disease) and 114 healthy control subjects were recruited. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS: In 114 healthy control subjects, the frequency of the mutant T allele was 38.0%, comparable to that of a Hong Kong (Chinese) population. The genotype distribution did not differ between control subjects and type 2 diabetic patients (chi(2) = 3.67, P > 0.05). Genotypic analysis revealed that type 2 diabetic patients with CHD displayed a greater prevalence of T allele (45.2%) than type 2 diabetic patients without CHD (30.4%) (chi(2) = 8.72, P < 0.005). The odds ratio for CHD in type 2 diabetic patients in presence of T allele was 1.89 (CI 95%, 1.24-2.88). The MTHFR genotype were different between diabetic patients with and without CHD (chi(2) = 11.98, P < 0.005). Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotype or CC plus CT genotype. CONCLUSIONS: The C677T mutation of MTHFR gene is common in the Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels could constitute a useful predictive marker for CHD in Chinese type 2 diabetic patients.     

亚甲基四氢叶酸还原酶基因C677T多态性与原发性高血压患者动脉顺应性的关系

目的研究亚甲基四氢叶酸还原酶基因C677T多态性与原发性高血压及动脉顺应性的关系。方法对695例原发性高血压患者和509例年龄匹配的正常对照者采用聚合酶链反应和限制片长多态性分析方法进行基因多态性分析,电泳判断基因型及测序,并测定颈动脉—桡动脉脉搏波速度和颈动脉—股动脉脉搏波速度。结果高血压组TT基因型频率和T等位基因频率显著高于正常对照组(26.5%比20.6%及48.7%比42.4%,P=0.015和0.002)。T等位基因携带者的颈动脉—股动脉脉搏波速度显著高于CC基因型者(P<0.05),高血压组颈动脉—桡动脉脉搏波速度在T等位基因携带者也显著高于CC基因型者(P=0.001)。携带T等位基因的高血压患者颈动脉—股动脉脉搏波速度及非单纯收缩期高血压患者颈动脉—桡动脉脉搏波速度均显著高于CC基因型者(P<0.05)。结论亚甲基四氢叶酸还原酶基因C677T多态性可能与原发性高血压发病危险性增加有关,并且677T等位基因可能是高血压动脉硬化的遗传因素。     

Mild hyperhomocysteinemia,C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study

The role of hyperhomocysteinemia as a risk factor for diabetic long-term complications has not been sufficiently evaluated in prospective studies, considering specific correlates of homocysteine (tHcy) concentration and traditional cardiovascular disease (CVD) risk factors. Fasting tHcy, vitamin B12 and folate plasma levels, the common methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, as well as clinical and lifestyle information were assessed in 216 type 2 diabetic patients attending two outpatient clinics, who had a follow-up evaluation at 65 ± 9 months for the incidence of macroangiopathy. At basal evaluation, mild hyperhomocysteinemia (tHcy ≥ 15 μmol/l) was diagnosed in 21.3% of participants. At follow-up, hyperhomocysteinemia and the distribution of MTHFR C677T genotype did not significantly differ according to the incidence of macroangiopathy. Multiple variables adjusted ORs (95% CI) for CVD associated with mild hyperhomocysteinemia were 1.01 (0.37–2.82); P > 0.05; those associated with MTHFR TT genotype were 0.46 (0.15–1.38); P > 0.05. Although the prevalence of hyperhomocysteinemia was higher in diabetic men (26.9%) than in women (16.1%; P > 0.05), similar results were also observed in a separate sex-analysis. At the multivariate analysis, including in the model other potential CVD risk factors, only creatinine clearance was a significant risk factor for the development of macroangiopathy. In this cohort of diabetic subjects, mild hyperhomocysteinemia and the MTHFR TT genotype are not significant risk factors for the development of macroangiopathy; impaired renal function was confirmed as a significant predictor of this complication.     

MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients

Point mutations in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were implicated in the pathogenesis of diabetic nephropathy (DN) in many ethnic groups. This study addressed the association of C677T and A1298C single nucleotide polymorphisms (SNPs) of MTHFR gene with DN in Tunisian type 2 diabetes (T2DM) patients. Study subjects comprised 93 DN patients, 267 patients with normoalbuminuria, and 400 control subjects. C677T and A1298C genotypes were determined by PCR-RFLP analysis, and homocysteine levels were measured by ELISA. A1298C and C677T were highly prevalent among T2DM patients, with allele frequencies of 0.26 and 0.36, respectively. Higher mutant 677T allele and 677C/T and 677T/T genotypes of C677T SNP, but not A1298C SNP, together with 677C/1298A, 677C/1298C, and 677T/1298A haplotypes were seen in DN patients compared to normoalbuminuric patients, (p<0.001). Plasma homocysteine was positively associated with MTHFR 677T/T genotype among the three groups, and was significantly elevated in double heterozygous DN patients but not in normoalbuminuric patients or controls. Logistic regression analysis with DN as dependent variable showed that homocysteine (OR, 1.153) and MTHFR 677T/T (OR, 9.799) were the only variables associated with DN, after adjusting for possible confounding variables. C677T, but not A1298C, SNP, is a risk factor for DN, presumably acting by elevating homocysteine levels.     

动脉粥样硬化性脑梗死的亚甲基四氢叶酸还原酶基因多态性研究

目的　探讨亚甲基四氢叶酸还原酶 (MTHFR)基因C6 77T多态性与动脉粥样硬化性脑梗死的关系。方法　采用聚合酶链式反应和限制片断长度多态性 (PCR RFLP)技术 ,检测 6 2例动脉粥样硬化性脑梗死患者和 79名健康对照者的C6 77T突变的基因型。结果　MTHFR基因C6 77T突变型等位基因 (V)频率在患者组和对照组间比较 ,差异有显著性意义 (χ2 =4.41,P <0 .0 5 ) ;3种基因型频率在两组人群中差异均无显著性意义。基因型频率的相对危险分析 ,AV基因型比AA基因型患脑梗死的危险高 1.76倍 ;VV基因型比AA基因型患脑梗死的危险高 3.2 5倍。结论　MTHFR基因C6 77T突变型等位基因与动脉粥样硬化性脑梗死有一定的关联 ,突变基因型增加了动脉粥样硬化性脑梗死的发病危险     

冠心病患者亚甲基四氢叶酸还原酶基因多态性87例研究

目的探讨N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与冠心病的关系。方法对2003年11月至2005年8月贵阳医学院附属医院及贵州市第二人民医院住院的87例冠心病患者(冠心病组)及同期在门诊进行健康体检的73名健康人(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测其MTHFRC677T基因多态性。结果对照组与冠心病组MTHFR677位T等位基因的分布频率分别是18.5%,36.1%,病例组MTHFR基因C677T的CT基因型及T等位基因频率显著高于对照组,差异有显著性(P<0.05)。结论MTHFRC677T基因多态性与冠心病密切相关。     

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。     

Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension relation: with the development of hypertensive end-stage renal disease

BACKGROUND: The pathogenesis of hypertensive nephropathy is multifactoral and in addition to BP, other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include genetic predisposition and increased pleasure level of homocysteine-intermediate protein catabolism product known to induce kidney injury. The 677C --> T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated homocysteine level in the general population, and therefore it has been hypothesized to be a risk factor for the development of renal failure in the course of essential hypertension. METHODS: In this case-control, cross-sectional study the frequency of the MTHFR 677C --> T and the 1298A --> C polymorphism was compared between patients with hypertension-related chronic renal failure (n = 90), patients with essential hypertension without kidney injury (n = 90), and healthy individuals (n = 90) who were matched for age and gender. In addition, the influence of these polymorphisms on homocysteine concentration in individuals with essential hypertension was examined. RESULTS: The frequency of the MTHFR 677 TT genotype did not differ between groups (4.5%, 12.3%, and 11.1%, respectively). Patients with hypertension and the 677TT genotype showed significantly higher homocysteine levels as compared to individuals having CC and CT. In the multivariate correlation analysis the MTHFR 677TT genotype (P < .01; beta = 0.27), age (P < .001; beta = 0.33), and body mass index (P < .01; beta = 0.3) were independent predictors for total homocysteine level. CONCLUSIONS: Plasma homocysteine levels in individuals with essential hypertension is affected by the MTHFR 677C --> T polymorphism. However, we did not prove the hypothesis that MTHFR 677C --> T influences the risk of development of renal failure in the course of hypertension.     

亚甲基四氢叶酸还原酶基因多态性与2型糖尿病微血管病变易感性的研究

目的 探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR)基因多态性与中国北方汉族2型糖尿病患者微血管并发症（DMAP）易感性的关系。方法 应用聚合酶链反应－限制性片段长度多态性（PCR－RFLP）的方法检测291名中国北方汉族[2型糖尿病患者229例,其中无微血管并发症（NCD）组102例,糖尿病视网膜病变（DR）组60例,糖尿病肾病（DN）组和67例;健康人对照（CON）组62例]MTHFR基因的多态性,比较各组间MTHFR等位基因和基因型的频率。结果 基因型BB在DN及DR组（34．3％和31．7％）高于NCD组和CON组（13．7％和12．9％）;DN及DR组的等位基因B频率（54．4％和59．9％）,也高于NCD组和CON组（41．2％和35．5％）,差异均有显著性意义。基因型BB和等位基因B在NCD和CON组之间的分布无统计学差异。结论 MTHFR基因C677T变异与中国北方汉族2型DM患者DMAP的发生有关。等位基因B可能是DMAP的易感基因。     

亚甲基四氢叶酸还原酶基因677和1298位点多态性与溃疡性结肠炎的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T和A1298C位点多态性与浙江汉族人群溃疡性结肠炎(UC)的关系.方法 采用限制性片段长度多态性PCR(PCR-RELP)法,在274例UC患者和726例正常对照者中检测MTHFR C677T及A1298C基因多态性分布差异.结果 UC患者中,MTHFR C677T突变等位基因(T)和基因型(CT+TT)频率与正常对照组相比差异无统计学意义(P＞0.05);而MTHFR A1298C突变等位基因(C)和基因型(AC+CC)频率均高于正常对照组(35.77%比29.96%,P=0.013;52.19%比44.90%,P=0.039).另外,MTHFR 677纯合子突变基因型(TT)、突变等位基因(T)以及677CT/1298AC复合基因型频率在广泛性结肠炎患者中明显高于远端结肠炎(37.66%比14.72%,P=0.0002;49.35%比32.99%,P=0.0004;29.87%比15.23%,P=0.006);重度UC患者的MTHFR 1298位点突变等位基因(C)频率显著低于(轻+中)度患者(18.97%比33.88%,P=0.022).结论 MTHFR C677T及A1298C基因多态性与浙江汉族UC明显相关.

Abstract：

Objective To investigate the association between the genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and ulcerative colitis (UC) of Han ethnic population in Zhejiang, China. Methods Two hundred and seventy-four consecutive patients with UC and 726 healthy controls (HC) were studied. The genetic polymorphisms of MTHFR (C677T and A1298C) were genotyped using PCR-RELP methods. Results The frequencies of variant allele and genotype in MTHFR A1298Cgene were higher in UC patients than in the HC (35.77% vs 29. 96%, P =0. 013; 52. 19% vs 44. 90%,P=0.039; respectively). However, there were no significant discrepancies of the allele and genotype frequencies in the MTHFR C677T gene between the UC patients and the HC (P ＞ 0. 05 ). In addition, the MTHFR 677Tr homozygote, T allele and 677CT/1298AC compound genotype were more prevalent in patients with extensive colitis than in those with distal colitis (37. 66% vs 14. 72% ,P = 0. 0002; 49. 35% vs 32.99% ,P =0. 0004; 29. 87% vs 15.23% ,P =0. 006; respectively). Furthermore,the variant allele in the MTHFR A1298C gene (C) in severe UC patients was significantly lower than in mild and moderate UC patients (18.97% vs 33. 88% ,P =0. 022). Conclusion The genetic polymorphisms of MTHFR C677T and A1298C are obviously associated with Han ethnic population with UC in Zhejiang province.     

Serum Homocysteine,MTHFR Gene Polymorphism,and Carotid Intimal-Medial Thickness in NIDDM Subjects

We assessed the contribution of serum homocysteine levels, an independent risk factor for vascular disease, and of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation to the variability of carotid intimal-medial thickness (IMT) in patients with non–insulin-dependent diabetes mellitus (NIDDM). Ninety-five patients (33 males and 62 females, mean age 53 ± 10 years) without nephropathy or other vascular complications were enrolled. Fasting total serum homocysteine and other biochemical analytes were measured. The MTHFR polymorphism was determined by the polymerase chain reaction. Common carotid IMT and plaques or stenoses in the carotid district were measured by ultrasonography. Serum total homocysteine concentrations were higher in subjects with the mutant (Val/Val) genotype than in those with the Ala/Val plus Ala/Ala genotypes (P = 0.02). On univariate analysis, carotid IMT was significantly associated with age, body mass index (BMI), systolic blood pressure, and total cholesterolemia. No significant association was found between IMT and serum homocysteine or the MTHFR polymorphism, although a slightly greater IMT was observed in the homozygous Val genotypes. On multiple regression analysis, only age and BMI were independently associated with IMT and explained about 40% of IMT variability. The results did not change when the analysis was restricted to the subgroups with or without atherosclerotic plaques in the carotid district. In 95 Italian NIDDM patients without nephropathy, neither basal levels of serum total homocysteine nor the MTHFR C677T polymorphism predicted significant changes in common carotid intimal-medial thickness.     

Diabetic retinopathy in Euro-Brazilian type 2 diabetic patients: relationship with polymorphisms in the aldose reductase,the plasminogen activator inhibitor-1 and the methylenetetrahydrofolate reductase genes

We investigated the relationship between diabetic retinopathy (DR) and three polymorphisms, C(-106)T in the aldose reductase (ALR2) gene, 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene and C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, in 210 Euro-Brazilian type 2 diabetic patients. Retinopathy was evaluated by funduscopic examination and genotype analysis was performed using the polymerase chain reaction and allele-specific restriction. Retinopathy was detected in 47% of the patients. There were no significant differences in allele or genotype distributions between patients with or without retinopathy for all polymorphisms. Thus, the three polymorphisms are not related to the presence of DR in Euro-Brazilian type 2 diabetic patients.     

基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究

目的 探讨基质金属蛋白酶9(MMP-9)基因C-1562T多态性与2型糖尿痫血管病变的关系．方法 运用PCR-RFLP检测110名健康对照者和450例2型糖尿病(DM)患者(其中单纯2型DM者100例、大血管病变者120例、糖尿病肾病(DN)患者130例、糖尿病视网膜病变患者100例)的MMP-9基因型，比较各组的基因型和等位基因频率。结果 (1)所有糖尿病视网膜病变患者的基因型均为CC型。(2)与对照组和单纯2型DM组相比，大血管病变组的T基因型和T等位基因频率显著升高，而DN组的TT基因型和T等位基因频率明显下降。(3)Logistic回归分析显示MMP-9 T等位基因、血清MMP-9、总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)是大血管病变发生的危险因素；尿白蛋白排泄率、脂蛋白(a)、HbA1C是DN发生的危险因素。结论 MMP-9基因C-1562T多态性与2型DM血管病变的发生有关，T等位基因是大血管病变的易感基因，是DN的保护基因。