Study of platelet activation,hypercoagulable state,and the association with pulmonary hypertension in children with β-thalassemia

Background

The increased survival rate of thalassemic patients has led to unmasking of management related complications which were infrequently encountered.

汉族脑卒中与N5,N10亚甲基四氢叶酸还原酶基因多态性的相关性研究

目的　探讨人体 N5,N1 0亚甲基四氢叶酸还原酶 (MTHFR)的基因多态性与脑卒中的遗传相关性。方法　采用限制性内切酶片段长度多态性方法 (PCR- RFLP) ,对 67例脑卒中病人和 78例健康人 MTHFR基因 C677T多态性位点进行检测。结果　病例组 MTHFR基因 T、C等位基因频率分别为 53%、47%,对照组为 39.7%、60 .3%,两组显著性差异 (χ2 =5.0 9,P<0 .0 5)。 TT型携带者较 CC型携带者罹患脑卒中的相对风险度为 2 .35(95%CI1 .0 2～ 5.43)。 T等位基因携带者较 C等位基因携带者罹患脑卒中的相对风险度为 1 .71 (95%CI1 .0 7～ 2 .74)。出血性卒中与缺血性卒中之间等位基因及等位基因型频率无明显差异。结论　脑卒中汉族人群 MTHFR基因 C677T位点多态性与脑卒中有相关性 ,MTHFR基因可能是脑卒中的一个易感基因。     

H型高血压患者代谢性相关指标及MTHFR基因多态性分析

目的探讨H型高血压患者代谢性相关指标以及与亚甲基四氢叶酸还原酶MTHFR多态性的关系。方法依托深圳南山区脑卒中社区综合防治项目,选取150例H型高血压患者和80例对照者,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测MTHFR基因多态性,同时测定同型半胱氨酸和代谢性相关指标。结果 H型高血压组中同型半胱氨酸、尿酸、肌酐水平明显高于普通高血压组(P0.01),且H型高血压组中CC、CT、TT不同基因型同型半胱氨酸水平差异显著,尤以TT基因型同型半胱氨酸水平最高,差异有统计学意义(P0.01)。结论尿酸、肌酐与H型高血压关系紧密,H型高血压人群中MTHFR基因677C/T纯合突变TT基因型可能是同型半胱氨酸升高的重要遗传因素,而MTHFR基因多态性与血糖、尿酸、肌酐、甘油三酯、总胆固醇、低密度脂蛋白无关。     

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Greek family

Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset inherited disease, characterised by recurrent strokes, migraine and cognitive impairment. We present the first Greek family with CADASIL, caused by the R153C mutation at exon 4 of the Notch3 gene. A member of this family carrying this mutation was also found to be heterozygotic for the MTHFR mutation, factor V Leiden mutation and had low serum levels of antithrombin III, thus resulting in the appearance of recurrent strokes and thrombotic episodes since his early adulthood. The co-existence of these thrombophilic disorders with CADASIL in a single person poses serious therapeutic dilemmas, as the administration of anticoagulant agents may correlate with increased risk of potentially fatal intracerebral haemorrhage.     

冠心病患者甲基四氢叶酸还原酶基因多态性的研究

目的 :探讨同型半胱氨酸(HCY)代谢相关酶甲基四氢叶酸还原酶 (MTHFR)基因多态性、血浆HCY、叶酸、维生素B12 水平与冠心病的关系。方法:用酶联免疫试剂盒测定血浆HCY ,放射免疫法测定维生素B12 和叶酸水平 ,以多聚酶链反应 -限制性内切酶片段长度多态性 (PCR -RFLP)分析MTHFRC677T基因型。结果:冠心病组MTHRR基因TT型、TC型及CC型频率分布及T、C等位基因频率与对照组无显著差异 (χ2=1.427,P>0.05;χ2=1.257,P>0.05)。冠心病组HCY水平为 (21.58±12.69)umol/L显著高于对照组(P<0.01)。叶酸浓度平均(2.78±1.66)ng/ml,维生素B 12 浓度平均 (231.76±143.78) pg/ml,明显低于对照组 (P<0.01)。冠心病组中3种基因型的HCY水平有显著差异 ,TT型HCY明显高于CC型 (P<0.05)。结论:高HCY血症是冠心病发病的危险因素 ,血浆HCY水平的升高与叶酸、维生素B12 的降低有关。MTHFR基因C677T的TT突变是高同型半胱氨酸血症的原因 ,但MTHFRC677T基因多态性与冠心病的发生无显著相关     

Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population

Background and purpose: The association of polymorphisms in the nitric oxide synthase 3 (NOS3) gene (T‐786C, variable number tandem repeats 4A/B/C, and G894T) and in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) with acute ischemic stroke have been reported. Methods: First‐time onset acute ischemic stroke patients (n = 120) and controls (n = 207) with no past history of stroke were compared. Allele specific gene amplification and restriction fragment length polymorphism (RFLP) analysis were used to determine the genotype and allelic frequencies in both groups. Plasma homocysteine (Hcy) and nitrite levels were measured. Results: No significant association of NOS3 polymorphisms with ischemic stroke was noted. The TT genotype of the MTHFR C677T polymorphism was significantly associated with ischemic stroke (P = 0.004). Elevated plasma Hcy levels were also significantly associated with ischemic stroke (P = 0.001). Conclusions: The TT genotype of C677T polymorphism in the MTHFR gene contributes to genetic susceptibility of acute ischemic stroke in a Singapore population.     

Dietary folate is associated with p16(INK4A) methylation in head and neck squamous cell carcinoma

Inactivation of the p16(INK4A) (CDKN2A) gene in the Rb pathway is among the most common somatic alterations observed in tobacco-related solid tumors, including head and neck squamous cell carcinoma (HNSCC). In addition, a low folate diet is an important risk factor for HNSCC. Decreased dietary folate in an animal model of hepatocellular carcinoma has been associated with the induction of epigenetic silencing of the p16(INK4A) gene. In an ongoing population-based study of HNSCC, we sought to extend this observation to human disease testing the hypothesis that p16(INK4A) methylation is associated with decreased dietary folate. We also investigated the association of methylation silencing with functional polymorphisms in the folate metabolism enzyme methylene tetrahydrofolate reductase (MTHFR). In 169 HNSCCs, the odds ratio for p16(INK4A) methylation among those with low dietary folate intake was 2.3 (95% CI = 1.1-4.8) when compared with those with high folate intake. Furthermore, this increased risk for epigenetic silencing at p16(INK4A) was modified by the MTHFR alleles previously associated with diminished serum folate levels. Hence, in HNSCC low dietary intake of folate is associated with p16(INK4A) methylation, and this relationship is modified by the MTHFR genotype. Our data provides important evidence for a mechanism of action of folate deficiency in cancer.     

The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer

We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients.     

Thrombophilic screening in young patients (< 40 years) with idiopathic ischemic stroke: a controlled study

Introduction

Despite extensive clinical and laboratory investigations, the etiology of ischemic stroke remains unknown in approximately one third of patients.

Materials and Methods

Thirty-four consecutive patients less than 40 years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented ischemic stroke underwent, one year after the acute event, laboratory evaluation of antithrombin, protein C, free and total protein S, activated protein C resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR) were also evaluated and compared to the results obtained in 120 normal controls.

Results

Antithrombin and protein C levels resulted normal in all cases. One patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had activated protein C resistance. Homocysteine levels above 15 μmol/L were found in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of 120 (1.66%) controls (OR = 95.31; 95% C.I.: 18.22-667.81). The multivariate analysis selected that the presence of APA was significantly associated with an increased risk of stroke (OR = 156.60; 95% C.I.: 25.99-943.47) in this cohort of patients. The combination between APA and cardiovascular risk factors determined a risk of 29-fold (OR = 29.31; 95% CI: 3.28-261.69).

Discussion

Our data suggest that the presence of APA is associated with an increased risk of idiopathic ischemic stroke in young patients. Furthermore, also the combination of APA and cardiovascular risk factors is significantly associated with development of idiopathic ischemic stroke.