An epidemiological study for the effect of inter-relationship between lifestyles and genetic factor on occurrence of stroke

生活方式与遗传因素对脑卒中发生影响的流行病学研究

• 批准号: 12470094
• 负责人: TANAKA Heizo
• 金额: $ 8.7万
• 依托单位: National Institute of Health and Nutrition (2001-2002)Tokyo Medical and Dental University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470094/
• 关键词: Stroke; Genotype; Risk factors; Blood pressure; Serum lipid; Lifestyles; Epidemiological survey; Physical activities; 横断研究; アルコール; 脂質代謝; コレステロールエステル転送蛋白; 疫学; 遺伝子多型; アンギオテンシン変換酵素遺伝子; アポリポ蛋白E遺伝子; コレステロールエステル変換酵素遺伝子; メチレンヒドロ葉酸還元酵素遺伝子; 一酸化窒素

We genotyped 832 healthy Japanese for a polymorphism of NOS3 in intron 4 (ecNOS4a/b), using the polymerase chain reaction method, and scored their habitual physical activity level by using the rate of energy expenditure per resting metabolic rate through an interview according to a semiquantitative assessment method. Only in the subjects who had the rarer a allele (aa+ba type), systolic blood pressure was found to be inversely correlated with physical activity level (P for linear trend=0.0496, for interaction=0.0071). Eventually, this polymorphism was significantly associated with the prevalence of systolic hypertension only in the subjects who were in the lowest tertile of physical activity level (OR=2.4, 95% CI, 1.1 to 5.6, P for interaction=0.0474).[Hypertension 2003]The genetic polymorphisms of ADH2 and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. A multiple linear regression analysis showed that the relationship be … More tween alcohol consumption and diastolic blood pressure was significantly stronger in men with ADH21/21 than those with ADH21/22 or 22/22 (adjusted regression coefficient = 0.0392 versus 0.0113 mmHg for + 1 g ethanol/week, P for difference in slope = 0.018). The strength of the alcohol-BP relationship was similar in all of the ALDH2 genotype groups. [J Hypertension 2003]We examined allele frequencies for the common cholesteryl ester transfer protein (CETP) TaqI polymorphisms and the associations of CETP-TaqI polymorphisms with serum lipid and lipoprotein levels taking into account for selected lifestyle factors in a well-characterized random sample of 527 healthy subjects. B2 allele frequency was 0.39 in men and 0.41 in women, and its presence was significantly associated with increased levels of HDL cholesterol (HDL-C) in men (P=0.003 for linear trend). A similar tendency in women was observed, although P value for trend did not reach 0.05. There were not significant interactions between TaqIB genotype and smoking and alcohol drinking or daily physical activity in HDL-C. There were no statistically significant differences among TaqIA genotype in lipid and lipoprotein levels. Multiple linear regression analysis showed that B1B2 and B2B2 explained 1.7% and 2.2%, and 0.6% and 1.0% of variation in men and in women in HDL-C, respectively. [J Epidemiology 2002]We conducted examined 455 Japanese rural residents to investigate the associations of plasma tHcy concentration with 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and selected life-style related factors. The frequency of the mutant allele, Valine (V) allele, was 0.40 and the prevalence of VV genotype was 14.3%. Plasma tHcy concentration in VV was significantly higher than those in two other genotypes. There were significant inverse associations of plasma tHcy with serum folate and serum vitamin B12 (P<0.001 for trend, respectively) ; both being stronger in VV than in other genotypes. The number of cigarettes smoked per day was positively associated with plasma tHcy concentration. A multivariate regression analysis revealed that serum folate, serum vitamin B12, and MTHFR genotype were independently associated with plasma tHcy. The inter-individual variance of plasma tHcy was more explained by serum folate and vitamin B12 than by MTHFR genotype. Higher intakes of folate, vitamin B12, and non-smoking may be important to prevent mild hyperhomocysteinemia and the eventual atherosclerotic diseases in this Japanese rural population. [J Epidemiology 2002] Less

我们使用聚合酶链反应方法对内含子4（ECNOS4A/b）中NOS3的多态性进行了基因分型，并使用了聚合酶链反应方法，并通过使用半涉及评估方法通过访谈的每次静止代谢率来评分其习惯性身体活动水平。仅在具有稀有等位基因（AA+BA类型）的受试者中，发现收缩压与体育活动水平成反比（线性趋势= 0.0496的P，相互作用= 0.0071）。最终，这种多态性仅与在体育活动水平最低的受试者中仅与收缩压的患病率显着相关（OR = 2.4，95％CI，1.1至5.6，相互作用的P = 0.0474。 （PCR-RFLP）方法。多次线性回归分析表明，与ADH21/21的男性相比，与ADH21/22/22或22/22的男性，这种关系是……更多的补间饮酒和舒张压更强（调整后的回归系数= 0.0392，对0.011113 mmhg，对于 + 1 g乙醇/周，在SLOPES中差异为 + 1 g乙醇，p。在所有ALDH2基因型组中，酒精BP关系的强度都是相似的。 [J Hypertension 2003]我们检查了普通胆固醇酯传递蛋白（CETP）TAQI多态性的等位基因频率，以及CETP-TAQI多态性与血清脂质和脂蛋白水平的CETP-TAQI多态性的关联，以考虑到良好character seplacter samply样本的52.健康样本中所选的生活方式。男性的B2等位基因频率为0.39，女性为0.41，其存在与男性的HDL胆固醇（HDL-C）水平升高显着相关（线性趋势P = 0.003）。尽管趋势的P值未达到0.05，但观察到女性的类似趋势。在HDL-C中，Taqib基因型与吸烟与饮酒或每日体育活动之间没有显着相互作用。在脂质和脂蛋白水平中，taqia基因型之间没有统计学上的显着差异。多个线性回归分析表明，B1B2和B2B2分别解释了男性和HDL-C女性变异的1.7％和2.2％和0.6％和1.0％。 [J流行病学2002]我们进行了455个日本粗糙居民，研究了血浆thcy浓度与5个，10-甲基苯基氢叶酸酸酯（MTHFR）基因的关联和所选的生命相关因素。突变等位基因（V）等位基因的频率为0.40，VV基因型的患病率为14.3％。 VV中的血浆THCY浓度显着高于其他两种基因型中的血浆浓度。血浆THCY与血清叶酸和血清维生素B12存在显着的逆关联（分别为p <0.001）；两者在VV中都比其他基因型要强。每天熏制的香烟数量与血浆THCY浓度呈正相关。多元回归分析表明，血清叶酸，血清维生素B12和MTHFR基因型与血浆THCY独立相关。血清叶酸和维生素B12比通过MTHFR基因型更能解释血浆THCY的个体间差异。较高的叶酸，维生素B12和非吸烟的摄入量对于预防温和的高型心脏病血症和最终在日本粗糙种群中的动脉粥样硬化疾病可能很重要。 [J流行病学2002]更少

项目成果

J Chen, T Yokoyama, K Saito, N Yoshiike, C Date, H Tanaka: "Association of Human Cholesteryl Ester Transfer Protein-TaqI Polymorphisms with Serum HDL Cholesterol Levels in a Normolipemic Japanese Rural Population"Journal of Epidemiology. (印刷中). (2002)

J Chen、T Yokoyama、K Saito、N Yoshiike、C Date、H Tanaka：“人胆固醇酯转移蛋白 TaqI 多态性与血脂正常的日本农村人口血清 HDL 胆固醇水平的关联”流行病学杂志（正在出版）。 (2002)

Kokubo Y, Chowdhury AH, Date C, Yokoyama T, Sobue H, Tanaka H: "Age-Dependent Association of Apolipoprotein E Genotypes with Stroke Subtypes in a Japanese Rural Population"Stroke. 31. 1299-1306 (2000)

Kokubo Y、Chowdhury AH、Date C、Yokoyama T、Sobue H、Tanaka H：“日本农村人口中载脂蛋白 E 基因型与中风亚型的年龄依赖性关联”中风。

Saito K, Yokoyama T, Yoshiike N, Date C, Yamamoto A, Muramatsu M, Tanaka H: "Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?"Journal of Hypertension. 21. 1097-1105 (2003)

Saito K、Yokoyama T、Yoshiike N、Date C、Yamamoto A、Muramatsu M、Tanaka H：“乙醇代谢酶是否会改变饮酒与血压之间的关系？”高血压杂志。

K Saito, T Yokoyama, N Yoshiike, C Date, A Yamamoto, M Muramatsu, H Tanaka: "Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?"Journal of Hypertension. (印刷中).

K Saito、T Yokoyama、N Yoshiike、C Date、A Yamamoto、M Muramatsu、H Tanaka：“乙醇代谢酶是否会改变饮酒与血压之间的关系？”高血压杂志（正在出版）。

Kimura T, Yokoyama T, Matsumura Y, Yoshiike N, Date C, Muramatsu M, Tanaka H: "NOS3 Genotype-Dependent Correlation Between Blood Pressure and Physical Activity"Hypertension. 41. 355-360 (2003)

Kimura T、Yokoyama T、Matsumura Y、Yoshiike N、Date C、Muramatsu M、Tanaka H：“血压与体力活动之间的 NOS3 基因型依赖性相关性”高血压。