白介素6基因启动子区多态性与体重指数和炎症因子等生化指标的相关性及与冠心病发生发展关系的探索

Correlation of Polymorphism in IL-6 Gene Promoter with BMI,Inflammatory Factors,and Pathogenesis and Progression of CHD

本研究旨在通过对中国北方地区汉族人IL-6基因启动子区-572G/C,-597G/A多态性与体重指数(BMI)和炎症因子等生化指标的相关性的调查,探索基因多态性与冠心病(CHD)发生发展的关系。采用荧光杂交探针、以荧光共振能量转移原理和熔点曲线分析技术,测定了194例冠心病患者和123例健康对照者的IL-6基因型,同时测定BMI、超敏C反应蛋白(hsCRP)、血脂、载脂蛋白等指标,并通过建立逻辑回归(Logistic regression)模型分析CHD发生的危险因素。结果表明,在所有观察对象中发现中国北方汉族人IL-6基因启动子区-597位点有7例为GA型,其余均为GG型,尚未发现AA型,未发现其多态性与BMI和炎症因子等生化指标的相关性。冠心病(coronary heart disease,CHD)组与对照组-572G/C基因型频率和等位基因频率分布差异无统计学意义,但是CHD组和对照组携带G等位基因和非G等位基因频率相比差异有统计学意义(P=0.0425)。正常对照组中携带G等位基因者收缩压中位数水平明显高于非G等位基因者(P=0.02)。在所有研究对象中,与非G等位基因组相比,携带G等位基因组的体重指数、超敏C反应蛋白、收缩压中位数水平显著升高(P值分别为0.026、0.022、0.005)。经Lo-gistic逐步回归分析显示,年龄、血清甘油三脂、性别、高血压、载脂蛋白C2、血清总胆固醇、脂蛋白a是冠心病发生的危险因子,而载脂蛋白A1是保护因子(P<0.05),未见-572G/C的G等位基因是一独立的危险因素。结论:IL-6基因启动子区-597G/A多态性和CHD的易感性无关,而-572G/C多态性与CHD的易感性有关,其机制可能与-572G/C多态性可导致BMI、hsCRP和血压的变化有关。

This study was aimed to explore the correlation between IL-6 gene promoter polymorphisms and coronary heart disease （CHD） by investigating the polymorphisms （-572G/C, -597G/A） in IL-6 gene promoter area, body mass index （ BMI）, inflammatory factors and other biochemical parameters in Han nationality of North China. The genotypes of IL-6 gene promoter-572G/C, -597G/A were detected by fluorescent probe hybridization with fluorescent resonance energy transfer and melting curve techniques in 194 CHD patients and 123 healthy people as control. The effects of genotype on plasma lipids, apoproteins, high sensitive C-reactive protein（hsCRP） and BMI were also studied. Logistic regression was performed to observe the risk factors of CHD. The results indicated that genotype of IL-6 gene promoter -597G/A polymorphism in 7 cases were GA and were GG in others, whereas no AA genotype had been found and no associations between polymorphism of IL-6 gene -597G/A, BMI and inflammatory factors were found. No differences had been found between the frequencies of IL-6 gene -572G/C genotypes and alleles in CHD and control group. However, significant difference was found between the G allele carrier （ GG ＋ GC） and non-G allele carrier （ CC ） of CHD and control group （p =0. 0425）. In the control group, median levels of systolic blood pressure of G allele carrier were significant higher than non-G allele carrier （p = 0.02）. Among all the subjects, median levels of BMI, hsCRP and systolic blood pressure in the group of G allele carrier were significantly higher than that in the group of non-G allele carrier, p values were 0.026, 0.022, 0. 005 respectively. Multivariate logistic regression analysis showed that age,triglyceride, sex,high blood pressure, apoprotein C2, cholesterol and lipoprotein-a） were the risk factors for CHD, and apoprotein AI was a protective factor. The G allele of IL-6 gene -572G/C has been not found to be a risk factor for CHD. It is concluded IL-6 gene -597G/A polymorphism is not correlated with the susceptibility to CHD; IL-6 gene -572G/C polymorphism may be correlated with the susceptibility to CHD in Han nationality of North China, the mechanisms may be related with the changes of BMI, hsCRP and blood pressure levels resulted from the polymorphism of IL-6 -572G/C.