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亚甲基四氢叶酸还原酶基因 C677 T多态性与中国山东地区汉族人群缺血性卒中、高尿酸血症的相关性

Correlations of methylenetetrahydrofolate reductase gene C677T polymorphism w ith ischemic stroke and hyperuricemia in Chinese Han population in Shandong, China

摘要:

目的:探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因C677 T 多态性与中国山东地区汉族人群缺血性卒中、高尿酸血症的相关性。方法纳入山东地区汉族急性缺血性卒中患者和年龄、性别相匹配的对照者。采用聚合酶链反应扩增和芯片杂交显色技术检测MTHFR基因C677T 多态性,并测定血清尿酸浓度。结果共纳入山东地区汉族急性缺血性卒中患者145例和年龄、性别相匹配的对照者145名。缺血性卒中组糖尿病构成比(26.90%对6.89%;χ2=20.653,P<0.001)以及空腹血糖[(5.56±1.57)mmol/L对(5.01±1.11)mmol/L;t=-3.390, P=0.001]、高半胱氨酸[中位数,四分位数间距:18.2(16.30~22.55)μmol/L对15.20(12.10~17.85)μmol/L;Z=-6.323,P<0.001]和尿酸[43.0(361.60~490.45)μmol/L对285.9(267.00~346.25)μm o l/L;Z=-10.360, P<0.001]水平均显著高于对照组;缺血性卒中组 T T 基因型(42.07%对15.17%;χ2=25.673, P<0.001)和 T 等位基因(58.28%对34.48%;χ2=33.008, P<0.001)分布频率均显著高于对照组。多变量logistic回归分析显示,尿酸[优势比( odds ratio, OR)1.018,95%可信区间(confidence interval, CI)1.013~1.024;P<0.001]、TT 基因型(对CT 基因型, OR 6.774,95%CI 1.779~25.507;P=0.005)、高血压( OR 1.919,95%CI 1.013~3.636;P=0.045)、高半胱氨酸( OR 1.153,95%CI 1.059~1.258;P=0.001)为缺血性卒中的独立危险因素。将缺血性卒中组与对照组合并,共101例存在高尿酸血症,189例尿酸正常。高尿酸血症组糖尿病患者构成比(32.67%对11.64%;χ2=23.749, P<0.001)以及总胆固醇[(5.67±1.56)mmol/L对(5.10±1.33)mmol/L;t=-3.255,P<0.001]和高半胱氨酸[19.50(17.10~24.70)μmol/L对15.40(12.60~18.05)μmol/L;Z=-7.236,P<0.001]水平显著高于尿酸正常组,TT 基因型(55.45%对13.76%;χ2=56.409,P<0.001)和T等位基因(71.79%对32.54%;χ2=79.561,P<0.001)分布频率显著高于尿酸正常组。多变量logistic回归分析显示,TT 基因型(对CC 基因型,OR 6.434,95%CI 2.334~17.736;P<0.001)、CT 基因型(对CC基因型,OR 2.234,95%CI 1.019~4.898;P=0.045)、高半胱氨酸(OR 1.081,95%CI 1.010~1.157;P=0.024)、总胆固醇(OR 1.363,95%CI 1.123~1.653;P=0.002)为高尿酸血症的独立危险因素。结论 MTHFR基因C677T TT 基因型和血清尿酸水平是中国山东地区汉族人群缺血性卒中的独立危险因素,MTHFR基因C677T TT 基因型亦为该人群高尿酸血症的独立危险因素,调整饮食习惯可能对山东地区汉族人群缺血性卒中的预防具有积极意义。

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abstracts:

ObjectiveToinvestigatethecorrelationsofmethylenetetrahydrofolatereductase(MTHFR) gene C677T polymorphism w ith ischemic stroke and hyperuricemia in Chinese Han population in Shandong, China.Methods The patients w ith acute ischemic stroke and age-and sex-matched controls in Chinese Han population in Shandong, China w ere enrol ed. Polymerase chain reaction amplification and microarray hybridization w ere used to detect the MTHFR gene C677T polymorphism, and the serum uric acid concentration w as measured. Results A total of 145 patients w ith acute ischemic stroke and 145 age-and sex-matched controls in Chinese Han population in Shandong, China were enroled. The proportion of diabetes ( 26.90%vs. 6.89%; χ2 = 20.653, P< 0.001 ) and fasting blood glucose ( 5.56 ± 1.57 mmol/L vs.5.01 ±1.11 mmol/L;t= -3.390, P=0.001), homocysteine (median, interquartile range:18.2[16.30-22.55 μmol/L] vs.15.20[12.10-17.85 μmol/L]; Z= -6.323, P<0.001), and uric acid (43.0[361.60-490.45 μmol/L] vs.285.9[267.00-346.25 μmol/L]; Z= -10.360, P<0.001) levels in the ischemia stroke group w ere significantly higher than those in the control group. The distribution frequencies of TT genotype (42.07%vs.15.17%; χ2 =25.673, P<0.001) and T alele (58.28%vs. 34.48%; χ2 =33.008, P<0.001) in the ischemia stroke group w ere significantly higher than those in the control group. Multivariate logistic regression analysis showed that the uric acid (odds ratio [OR] 1.018, 95%confidence interval [ CI] 1.013-1.024; P<0.001), TT genotype ( vs.CT genotype OR 6.774, 95%CI 1.779-25.507; P=0.005), hypertension ( OR 1.919, 95%CI 1.013-3.636; P=0.045), and homocysteine (OR 1.153, 95%CI 1.059-1.258;P=0.001) w ere the independent risk factors for ischemic stroke. The ischemic stroke group w as combined w ith the control group, a total of 101 patients had hyperuricemia, and 189 had normal uric acid. The proportion in patients w ith diabetes ( 32.67%vs. 11.64%; χ2 = 23.749, P< 0.001), as wel as total cholesterol ( 5.67 ±1.56 mmol/L vs.5.10 ± 1.33 mmol/L; t= -3.255, P< 0.001 ) and homocysteine ( 19.50[17.10-24.70 μmol/L] vs. 15.40[12.60-18.05 μmol/L ]; Z= -7.236, P< 0.001 ) levels in the hyperuricemia group w ere significantly higher than those in the normal uric acid group. The distribution frequencies of the TT genotype (55.45%vs.13.76%;χ2 =56.409, P<0.001) and T alele (71.9%vs.32.54%;χ2 =79.561, P<0.001) w ere significantly higher than those in the normal uric acid group. Multivariate logistic regression analysis show ed that the TT genotype ( vs.CC genotype, OR 6.434, 95%CI 2.334-17.736; P<0.001 ), CT genotype ( vs.CC genotype, OR 2.234, 95%CI 1.019-4.898; P= 0.045 ), homocysteine ( OR1.081, 95%CI 1.010-1.157;P=0.024), and total cholesterin ( OR 1.363, 95%CI 1.123-1.653;P=0.002) w ere the independent risk factors for high hyperuricemia. Conclusions MTHFR gene C677T TT genotype and serum uric acid level are the independent risk factors for ischemic stroke in Chinese Han population in Shandong, China. MTHFR gene C677T TT genotype is also an independent risk factor for hyperuricemia in this population. Adjusting dietary habit may have a positive significance for the prevention of ischemic stroke in Chinese Han population in Shandong, China.

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作者: 魏守超 [1] 刘志辉 [1] 刘君玲 [1]
栏目名称: 临床研究
DOI: 10.3760/cma.j.issn.1673-4165.2016.11.005
发布时间: 2017-03-17
基金项目:
山东省自然科学基金(ZR2015HL042) 潍坊市科技技术发展计划项目(2015WS050) 潍坊市卫生局科技项目(2014039)Fund programsShandong Natural Science Foundation of China Weifang science and technology development Planning Project, Shandong, China Weifang Health Bureau Science and Technology Project, Shandong, China
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