Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke

Background

The role of platelets and important effect modifiers on the risk of first stroke is unknown.

亚甲基四氢叶酸还原酶与肺癌的关联性研究

目的研究中国大陆人群亚甲基四氢叶酸还原酶（MTHFR）基因遗传位点C677T和A1298C多态性与肺癌的关联性。方法通过PubMed和CNKI等数据库检索有关MTHFR基因与肺癌的文献,收集和整理中国大陆人群MTHFR基因遗传位点C677T和A1298C与肺癌有关4 781例数据,进行Meta分析和关联性研究。结果 MTHFR基因遗传位点C677T的等位基因分布和基因型分布对应的假设检验的概率分别为2.6×10-3、9.4×10-3,表明病例对照差异有统计学意义（P〈0.05）;Meta分析对等位基因T的优势比OR值（95%CI）为1.28（1.16～1.41）。遗传位点A1298C的等位基因分布对应的假设检验概率分别为0.713和0.944,说明假设检验差异无统计学意义（P〉0.05）,Meta分析对等位基因A的优势比OR值（95%CI）为1.04（0.85～1.27）。结论 MTHFR基因的单核苷酸C677T多态性是中国大陆人群肺癌的遗传变异位点,A1298C多态性不是中国大陆人群肺癌的风险因素。     

Physical activity modulates effects of some genetic polymorphisms affecting cardiovascular risk in men aged over 40 years

BACKGROUND AND AIM: Several genetic polymorphisms have been found to be involved in cardiovascular risk, and many studies have documented the beneficial effect of systematic physical activity (PA) on the cardiovascular system. Our aim was to investigate the interactive effects of PA and genetic background on plasma lipids and homocysteine (tHcy) levels. METHODS AND RESULTS: Clinical and metabolic parameters, dietary intakes and some polymorphisms of the genes involved in cardiovascular risk (Apo E, fatty acid binding protein-2, Apo AII, hepatic lipase and methylene tetrahydrofolate reductase) were determined in 100 men aged over 40 years who cycle 120-150 Km/week and 100 age-matched sedentary controls. The physically active subjects had lower concentrations of plasma LDL cholesterol (LDL-C), triglyceride (TG), Apo B, glucose and tHcy, and higher concentrations of plasma HDL cholesterol (HDL-C) and Apo AI than the sedentary men; they also had larger LDL particle sizes (LDLs). The LDL-C and Apo B raising effect of the Apo E epsilon 4 allele detectable in the sedentary subjects was totally absent in the cyclists, in whom the LDL-C and Apo B lowering effect of the epsilon 2 allele was observed. PA blunted the TG-raising effect of the Apo AII-265TT genotype, and amplified the HDL-C raising effect of the HL-250AA genotype. PA had a small but significant lowering effect on plasma tHcy adjusted for folate levels in subjects with the 677TT genotype of the MTHFR gene. CONCLUSIONS: Extended high-intensity PA in men aged over 40 years may modify their metabolic cardiovascular risk factors even in the presence of some unfavourable genotypes.     

The methylenetetrahydrofolate reductase gene C677T polymorphism in patients with homozygous sickle cell disease and stroke

Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism may cause hyperhomocysteinaemia, a recognized risk factor for stroke, in individuals with folate deficiency. Homozygous sickle cell (SS) disease is associated both with increased demands for folic acid and a tendency to develop stroke. We therefore investigated a possible role of the MTHFR C677T polymorphism in SS disease patients with stroke. Investigation of the frequency of the polymorphism in 48 patients with stroke and in 48 age-, sex- and racially-matched SS controls without stroke failed to reveal a difference between the groups (Fisher exact test, P = 0.99). Homozygosity for the MTHFR C677T polymorphism is unlikely to be a risk factor for stroke in this population with SS disease.     

Prevalence of thrombotic risk factors among β-thalassemia patients from Western Iran

Background There is evidence for increased risk of thrombosis in patients with β-thalassemia intermedia and β-thalassemia major. The present study investigated the prevalence of thromboembolic risk factors of prothrombin G20210A, factor V Leiden G1691A and methylentetrahydrofolate reductase (MTHFR) C677T, as well as the hematological and clinical profiles in β-thalassemia major and intermedia patients from Western Iran. Methods Patients consisted of 158 β-thalassemia patients, 151 β-thalassemia major and 7 β-thalassemia intermedia patients, including 82 males and 76 females aged 13.6 ± 6.3 years. The control group were 180 healthy blood donors and school students, consisting of 103 males and 77 females aged 16.8 ± 2.1. Genotyping was done by PCR-RFLP using Mnl I, Hind III and Hinf I for factor V Leiden and prothrombin G20210A and MTHFR, respectively. Results The prevalence of prothrombin G20210A variant in patients and healthy individuals were 1.3 and 3.3%, respectively. Factor V Leiden G1691A was insignificantly higher in β-thalassemia patients (prevalence 5.7% and allele frequency 3.2%) compared to healthy individuals (2.8%). This mutation was found in eight β-thalassemia major (5.3%) and one β-thalassemia intermedia (14.3%) patients. The prevalence of MTHFR C677T polymorphism was slightly higher in patients (50%) compared to healthy individuals (48.3%). Around 71% of β-thalassemia intermedia and 38.4% of β-thalassemia major patients had undergone splenectomy. In β-thalassemia major patients, 5.3% had insulin dependent diabetes mellitus (IDDM) and 6.6% had HCV antibodies. All patients with IDDM were splenectomized and in one of them the prothrombin G20210A variant was found. Two patients, a 7-year-old boy with β-thalassemia intermedia receiving regularly blood transfusion and a β-thalassemia major patient (a 22-year-old splenectomized female), were found to be homozygous for MTHFR 677TT and heterozygous for factor V Leiden G1691A. Double heterozygosity for factor V Leiden G1691A and MTHFR C677T and also homozygous factor V Leiden 1691AA were found in two β-thalassemia major patients. No thromboembolic event has been recorded in the files of patients. Conclusions The results of present study establish the prevalence of biological risk factors of thrombosis in β-thalassemia patients from Western Iran. It seems that thrombophilic mutations may not be associated with thrombotic events in thalassemic patients, which needs to be confirmed by the study of larger sample sizes.     

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。     

非综合征型唇腭裂与新疆维吾尔族、汉族 MTHFR 基因多态性的研究

目的：探讨新疆维吾尔族、汉族非综合征型唇腭裂与 MTHFR 基因多态性的关系和民族差异。方法：170例 NSCL／P儿童患者和100例健康儿童对照,SNaPshot 分型方法检测 rs1801131、rs1801133位点多态性,分析基因型、等位基因频率和2个位点联合作用与 NSCL／P 的关系以及民族间差异。结果：rs1801133TT 与 T 等位基因在维、汉两民族间有统计学差异（P ＜0．05）;rs1801133CT 与 CT ＋TT 基因型在总病例组和总对照组间均有统计学差异（P ＜0．05）;rs1801131和 rs1801133的联合分析在维族内、汉族内、两民族间、维汉总人群中病例组和对照组均有统计学差异（P ＜0．05）;rs1801131多态性在维族内、汉族内、两民族间以及维汉总人群中均无统计学差异（P ＞0．05）。结论：rs1801133TT 与 T 等位基因的汉族比维吾尔族更易罹患 NSCL／P;rs1801131AC 和 rs1801133CC 联合作用与 NSCL／P 相关且维吾尔族罹患风险高于汉族;rs1801131多态性与 NSCL／P 不相关并无民族差异;rs1801133CT 与 CT ＋TT 基因型均是避免疾病的保护因素。     

Physical activity is inversely associated with total homocysteine levels, independent of C677T MTHFR genotype and plasma B vitamins

The homocysteine level is considered to be a product of genetic and lifestyle interactions, mainly mutated methylenetetrahydrofolate reductase (MTHFR) and the intake of folate, vitamin B12 and pyridoxine, and their blood levels. Physical activity has been associated with lower homocysteine levels in some population studies, especially among elderly subjects. To further elucidate the observed association between homocysteine and physical activity, while accounting for the effect of the MTHFR C677T genotype, and of plasma levels of folate and B12 vitamins, a cross-sectional study of 620 males and females, aged 70.5 ± 6.8 years, was carried out. Information on lifestyle habits was collected and laboratory examinations of 12-h fasting total plasma homocysteine, folate, and vitamin B12, as well as DNA analysis for MTHFR C677T variant, were performed. Median total homocysteine values were 11.4 μmol/l for males and 9.4 for females; p < 0.001. Smoking and ethnic origin were not found to be associated with homocysteine levels. Physically active subjects had significantly lower total homocysteine levels when adjusted for sex (p = 0.01). Significant inverse correlations were found between body mass index, plasma folate, B12 and homocysteine levels. Homocysteine levels of the CC, CT and TT genotypes were 9.7, 10.6 and 10.2 μmol/l, respectively (p = 0.002, controlling for sex). In a multiple linear regression model, a sedentary lifestyle increased homocysteine levels by 7% as compared to an active one (p = 0.03) controlling for sex, age, body mass index, folate, vitamin B12, and C677T genotype, all of which were also found to be significantly associated with homocysteine levels. Any level of physical activity was found to be independently associated with lower homocysteine levels in an elderly population, controlling for MTHFR genotype, plasma B-vitamins, age, sex, smoking and BMI. This study emphasizes the importance of maintaining a physically active lifestyle in the elderly.     

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。