肝脂酶基因启动子-250G／A多态性与2型糖尿病合并冠心病易感性的相关研究

Association of the hepatic lipase gene -250G/A promoter polymorphism with the susceptibility to type 2 diabetes mellitus combining with coronary heart disease

目的 探讨汉族人群肝脂酶（hepatic lipase，HL）基因启动子-250G／A多态性与2型糖尿病（type 2 diabetes mellitus，T2DM）合并冠心病（coronary heart disease，CHD）的相关性。方法 采用聚合酶链反应-限制性片段长度多态性方法（polymerase chain reaction-restricted fragment length polymorphism，PCR-RFLP）检测364例T2DM＋CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G／A多态性，并分析其对脂类的影响。结果 T2DM组与对照组HL基因启动子-250G／A多态性基因型和等位基因频率差异无统计学意义（P〉0．05）；T2DM＋CHD组GA＋AA基因型频率低于对照组（0．431vs0．618，P=0．031）；等位基因频率差异无统计学意义（P〉0．05）。调整混杂因素后，Spearman相关及线性回归分析，糖尿病患者（T2DM组和T2DM＋CHD组），A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关；Logistic回归分析显示，A等位基因是冠心病发生的一个危险因素。结论 HL基因启动子-250G／A多态性与2型糖尿病合并冠心病的发生有关，并影响脂类代谢。

Objective To investigate the association of hepatic lipase -250G/A gene promoter polymorphism with type 2 diabetes mellitus combining with coronary heart disease. Methods Using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）, we detected the genotypes of the hepatic lipase gene promoter -250G/A, the effect of this polymorphism on plasma lipids, lipoproteins and apolipoproteins in 364 patients with type 2 diabetes mellitus and coronary heart disease （T2DM＋CHD）, 357 patients with type 2 diabetes mellitus alone（T2DM） and 356 healthy controls. Results The frequencies of alleles and genotypes in the T2DM group were not significantly different from that of controls. However, the AA and GA genotypes in the T2DM＋CHD group were lower than those in controls （0. 431vs0. 618, P=0. 031）. The frequencies of both allele and genotype were not related to gender, family history, smoking and BMI. When adjusted by factors such as gender, age,BMI,history of smoking, family history of coronary atherosclerosis and systemic hypertension, Spearman＇s correlation and linear regression analyses showed that the A allele is related positively to the levels of HDL-C and apoA1 in T2DM and T2DM＋CHD patients. However,logistic regression analysis showed that the A allele is one risk factor for the presence of coronary heart disease. Conclusion The hepatic lipase gene promoter -250G/A polymorphisms is associated with type 2 diabetes mellitus with coronary heart disease, its polymorphisms may affect the levels of HDL-C and apoA1.