Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia

To investigate the role of methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, we analyzed the genotypes of MTHFR677 and MTHFR1298 of 130 schizophrenic patients and 226 controls, using a polymerase chain reaction restriction fragment length polymorphism method. The MTHFR T677 allele was significantly distributed (chi(2)=7.900; P=0.019), between schizophrenic cases and healthy controls. The T677T genotype was overrepresented in the schizophrenic patients (OR=2.504; 95% CI=1.276-4.915; chi(2)=7.477; P=0.006). The T677T/A1298A, and C677T/C1298C compound genotypes were greater in the schizophrenic patients (OR=3.157; 95% CI=1.522-6.545; chi(2)=10.336; P=0.001 and OR=1.744; 95% CI=0.108-28.121; chi(2)=0.158; P=0.691, respectively). The MTHFR T677 allele and T677T and T677T/A1298A genotypes are genetic risk factors for schizophrenia.     

皮质下缺血性血管性疾病的MTHFR基因多态性

目的研究皮质下缺血性血管性疾病(subcortical ischemic vascualar disease,SIVD)与N5,N10-亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因C677T多态性的关系。方法应用聚合酶链反应(polymerase chain reaction,PCR)技术和限制性酶切片段长度多态性(restriction fragment length polymorphism,RFLP)分析技术检测46例SIVD患者和43名正常人的MTHFR基因C677T多态性。结果 SIVD组T/T型、C/T型基因频率分别为36.96%、34.78%,分别高于对照组(20.93%、23.26%)。SIVD组T等位基因频率明显高于对照组(分别为54.35%、32.56%,P0.01)。T/T型、C/T型患SIVD风险度较C/C型分别高3.487倍(95%CI,1.1217～9.993)和2.954倍(95%CI,1.045～8.350)。结论 MTHFR基因T等位基因可能是SIVD的遗传易感因子,而C等位基因则具有一定保护作用,MTHFR基因C677T点突变与SIVD发病密切相关。     

Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients

BACKGROUND AND AIMS: In view of the prevailing controversy about the role of Methylenetetrahydrofolate reductase (MTHFR) C677T mutation in stroke and paucity of studies from India, this study has been undertaken to evaluate MTHFR C677T gene polymorphism in consecutive ischemic stroke patients and correlate these with folic acid, homocysteine (Hcy) and conventional risk factors. SETTINGS AND DESIGN: Ischemic stroke patients prospectively evaluated in a tertiary care teaching hospital. MATERIALS AND METHODS: Computerized tomography proven ischemic stroke patients were prospectively evaluated including clinical, family history of stroke, dietary habits and addictions. Their fasting and postprandial blood sugar, lipid profile, vitamin B12, folic acid and MTHFR gene analysis were done. STATISTICAL ANALYSIS: MTHFR gene polymorphism was correlated with serum folic acid, Vitamin B12 and Hcy levels; family history of stroke in first-degree relatives; and dietary habits; employing Chi-square test. RESULTS: There were 58 patients with ischemic stroke, whose mean age was 50 (4-79) years; among them, 10 were females. MTHFR gene polymorphism was present in 19 (32.8%) patients, 3 were homozygous and 16 were heterozygous. Both serum folate and B12 levels were low in 29 (50%) patients and Hcy in 48 (83%). Hypertension was present in 28 (48%) patients, diabetes in 12 (21%), hyperlipidemia in 52 (90%), smoking in 17 (29%), obesity in 1 (1.7%) and family history of stroke in first-degree relatives in 13 (22.4%). There was no significant relationship of MTHFR gene polymorphism with folic acid, B12, Hcy levels, dietary habits and number of risk factors. Vitamin B12 level was low in vegetarians (P<0.003). In 3 patients with MTHFR TT alleles, Hcy was elevated in all 3, low folic acid in 2 and family history of stroke in 1 patient. CONCLUSION: MTHFR gene polymorphism was found in one-third of patients with ischemic stroke and was insignificantly associated with higher frequency of elevated Hcy.     

TAFI gene polymorphisms in patients with cerebral venous thrombosis

Gene polymorphisms of thrombin activatable fibrinolysis inhibition (TAFI) factor have been investigated in various studies in terms of etiology (recurrence) and treatment (fibrinolytic effect) of thrombus formation. Cerebral venous thrombosis (CVT) is a life-threatening disease observed in young persons. Fifty-nine patients with CVT and 100 healthy control subjects were enrolled in the case/control study. The association between TAFI gene polymorphisms ?438G>A, +505A>G and +1040C>T and cerebral venous thrombosis was investigated. It was found that frequencies of polymorphic genotype and allele were not different in patients than in control group and that they were not significant for cerebral venous thrombosis.     

脂蛋白脂酶基因Ser447stop多态性与脑出血的关系

目的探讨脑出血与脂蛋白脂酶基因Ser447stop多态性相关性。方法采用聚合酶链反应和限制性片段长度多态性方法(PCR-RFLP法)来检测脂蛋白脂酶基因Ser447stop多态性,其中对照者66例,脑出血患者69例,测定所有样本的血脂水平。结果1、脑出血患者组CG基因型和G等位基因频率显著低于对照组(P<0.05);2、脑出血患者组血清TG、LDL-c水平较对照组高(P<0.01);同时CHO、ApoAⅠ、ApoB水平降低(P<0.01);3、CC基因型LDL-c含量较CG型高(P<0.05)。结论脂蛋白脂酶基因Ser447stop多态性与脑出血有一定关联,G等位基因可能是脑出血的一种保护性因素。     

Methylenetetrahydrofolate reductase gene and risk of Alzheimer's disease in Koreans

BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR) c.677C>T (A222V) polymorphism and Alzheimer's disease (AD) is controversial. The objectives of the study were to investigate the association between MTHFR c.677C>T polymorphism and AD in Korean elders and to the extent to which it is modified by the major components of one-carbon metabolism and apolipoprotein E (APOE) genotype. METHODS: Seven hundred and thirty-two community residents aged 65 or over were clinically assessed for AD. Genotyping was performed for MTHFR c.677C>T and APOE; serum levels of folate, vitamin B(12), and homocysteine were assayed. Age, gender and education were included as covariates. RESULTS: A trend of association between TT genotype of MTHFR c.677C>T and AD was found [adjusted OR (95% CI): 1.73 (0.80-3.74)]. The association was significant in the presence of below-median vitamin B(12) level [3.66 (1.14-11.71)] and in APOE e4 non-carriers [2.97 (1.00-8.55)] with significant interaction terms, and bordered on significance in the presence of above-median homocysteine level [2.73 (0.94-7.90)]. CONCLUSIONS: These findings suggest gene-environment and gene-gene interactions on the risk of AD in Koreans.     

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.     

Apolipoprotein H gene polymorphisms and risk of primary cerebral hemorrhage in a Chinese population

BACKGROUND AND PURPOSE: Apolipoprotein H (ApoH) has been implicated in several physiologic pathways including lipid metabolism, coagulation and the production of hypertension, which are related to the pathogenesis of primary cerebral hemorrhage (PICH). The gene coding for ApoH is polymorphic, with the occurrence of several common alleles in the general population. This genetically determined variation can effect lipid metabolism and the production of hypertension. We determined the distribution of ApoH gene polymorphisms in Chinese people and investigated whether these polymorphisms were associated with increased risk of PICH in a Chinese population. METHODS: We studied polymorphisms of the ApoH gene by the polymerase chain reaction-single strand conformation polymorphism technique and DNA sequencing in 140 PICH patients and 100 healthy control subjects. Serum antiphospholipid antibodies and lipid levels were also examined in all subjects. RESULTS: Four polymorphisms of the ApoH gene have been identified in Chinese people. No difference in genotype frequencies of G817T (Leu247Val) polymorphism, G1025C (Try316Ser) polymorphism and C1080T polymorphism was observed between PICH patients and control subjects (p > 0.05). The G341A (Ser88Asn) polymorphism correlated significantly with PICH. The frequencies of the A allele were significantly higher in PICH patients than in controls, especially in PICH patients with hypertension and a family history of stroke. CONCLUSIONS: Our results suggest that the G341A (Ser88Asn) polymorphism might be associated with increased risk of PICH in a Chinese population. The association appeared to be mediated by the generation of hypertension.     

Fibrinogen polymorphisms associated with sporadic cerebral hemorrhage in a Chinese population

Fibrinogen plays an important role in the intrinsic and extrinsic pathways of blood coagulation. This study investigated the association between common variants in the fibrinogen gene and the risk of developing sporadic cerebral hemorrhage (CH). We performed genotyping analyses for three single nucleotide polymorphisms (SNP) in the fibrinogen gene in a case-controlled study involving 195 patients with CH and 116 control participants; both groups were of southern Han-Chinese origin. Logistic regression analysis indicated that haplotypes ATA (rs1800790+rs1800787+rs6050), AA (rs1800790+rs6050) and TA (rs1800787+rs6050) could nearly double the risk of sporadic CH (odds ratio [OR]=1.738, 95% confidence interval [CI]: 1.103-2.740, p=0.017; adjusted OR=1.762, 95% CI: 1.042-2.982, p=0.035), although the three SNP were not associated with sporadic CH when analyzed separately. These findings indicate that rs1800790, rs1800787 and rs6050 polymorphisms may contribute to the etiology of sporadic CH in the Chinese population.     

甘肃地区汉族和回族脑出血患者α-内收蛋白基因rs4963多态性分析

目的 分析甘肃地区汉族和回族脑出血患者α-内收蛋白基因rs4963多态性的分布情况。方法 对甘肃地区汉族和回族脑出血患者各176例应用血液基因组DNA提取试剂盒方法检测α-内收蛋白基因rs4963多态性,比较rs4963多态性的分布差异。结果 汉族组和回族组α-内收蛋白基因rs4963基因型分布、等位基因频率均无明显差异(P>0.05); 按性别分层后汉族组与回族组基因型分布和等位基因频率仍均无明显差异(P>0.05)。结论 α-内收蛋白基因rs4963多态性在甘肃地区汉族和回族脑出血人群中无民族差异。     

Normal cerebral arteriography in patients with spontaneous subarachnoid hemorrhage

Previous studies have reported that 18 to 27% of patients with spontaneous subarachnoid hemorrhage have normal cerebral arteriograms. Our series of 220 patients from three hospitals demonstrated normal arteriograms in only 16 (7%). Recent improvements in neuroradiologic techniques, such as femoral catheterization, magnification angiography, oblique and basal projections, and subtraction most probably contribute to the improved yield. Nonvisualization of a cerebral aneurysm probably represents the most common explanation for a normal cerebral arteriogram.     

脑出血患者脑血流速度的观察

目的 观察脑出血后脑主要动脉的血流速度变化,进而研究脑血流动力学变化的临床价值。方法 采用经颅超声多普勒(transcranial Doppler,TCD)分别对216例脑出血患者和80名健康对照者的大脑中动脉、大脑前动脉、大脑后动脉、颈内动脉、基底动脉和椎动脉等颅内主要动脉的血流速度进行检测分析,记录包括收缩期峰速(Vs)、舒张期末流速(Vd)及搏动指数(PI)等血流参数及频谱形态。结果 脑出血组患者收缩期峰速与舒张末期流速与对照组比较均降低,差异有显著性意义(P<0.001)。脑出血组有164例患者(7.93％)颅内动脉血流速度降低,其中51例(23.61％)发生于脑出血早期,以舒张期末流速降低为主,113例(52.31％)发生于脑出血的中、后期,表现为普遍性流速降低。另有52例(24.07％)脑血流速度基本正常。结论 多数脑出血患者脑组织处于低循环状态,其程度与病情相关,因此对脑出血患者进行血流动力学监测有助于指导治疗及判断预后。     

Endothelial nitric oxide synthase gene polymorphisms predict susceptibility to aneurysmal subarachnoid hemorrhage and cerebral vasospasm.

Rupture of an intracranial aneurysm (subarachnoid hemorrhage) is a potentially devastating condition frequently complicated by delayed cerebral ischemia from sustained contraction of intracranial arteries (cerebral vasospasm). There is mounting evidence linking the formation of intracranial aneurysms and the pathogenesis of post-subarachnoid hemorrhage vasospasm to aberrant bioavailability and action of the vasodilator molecule nitric oxide generated by isoforms of nitric oxide synthase. In humans, the gene encoding the endothelial isoform of nitric oxide synthase (eNOS) is known to be polymorphic, with certain polymorphisms associated with increased cardiovascular disease susceptibility. In this prospective clinical study involving 141 participants, we used gene microarray technology to demonstrate that the eNOS gene intron-4 27-base pair variable number tandem repeat polymorphism (eNOS 27 VNTR) predicts susceptibility to intracranial aneurysm rupture, while the eNOS gene promoter T-786C single nucleotide polymorphism (eNOS T-786C SNP) predicts susceptibility to post-subarachnoid hemorrhage vasospasm. We believe that genetic information such as this, which can be obtained expeditiously at the time of diagnosis, may be used as a helpful adjunct to other clinical information aimed at predicting and favorably modifying the clinical course of persons with intracranial aneurysms.     

急性脑出血患者院内感染分析

目的 研究脑出血患者医院感染发生率及易感因素,应采取有效控制措施.方法 分析2000年1～12月在我院神经内科收治的脑出血患者96例的有关临床资料.结果 脑出血患者医院感染发生率为22.9%.肺部感染达95.4%.卧床、意识障碍程度、高龄、肺部基础病、食物反流是其易感因素.结论 积极控制肺部易感因素,提高机体抗病能力,对意识障碍病人早期抗炎治疗,是预防医院感染关键.     

急性脑出血患者院内感染分析

目的研究脑出血患者医院感染发生率及易感因素,应采取有效控制措施。方法分析2000年1~12月在我院神经内科收治的脑出血患者96例的有关临床资料。结果脑出血患者医院感染发生率为22.9%;肺部感染达95.4%。卧床、意识障碍程度、高龄、肺部基础病、食物反流是其易感因素。结论积极控制肺部易感因素,提高机体抗病能力,对意识障碍病人早期抗炎治疗,是预防医院感染的关键。