2型糖尿病的分子病因学研究

Study of molecule etiology in patients with type 2diabetes mellitus

目的探讨多个糖尿病易感基因在2型糖尿病发病中的作用及其与环境因素的关系。方法采用聚合酶链反应(PCR)技术,结合短串联重复序列(STR)多态性标记方法,对山东地区汉族107例2型糖尿病患者和105例正常对照者的GCK基因、N IDDM1(D 2S140)基因及小肠脂肪酸结合蛋白(FABP2)基因的多态性进行分析。结果GCK等位基因A 5及D 2S140等位基因B 2与2型糖尿病呈正相关(P<0.01);GCK等位基因A 1、A 3及D 2S140等位基因B 6与2型糖尿病呈负相关(P<0.01);FABP2各等位基因频率在两组分布未见显著性差异。2型糖尿病的发病与等位基因A 5及B 2、年龄、甘油三酯、载脂蛋白B及脂蛋白(a)呈显著正相关;与等位基因A 3及B 6呈显著负相关。结论GCK基因、N IDDM1(D 2S140)基因多态性与山东地区汉族2型糖尿病具有相关性,是2型糖尿病发病的危险因素。

Objective： To determine the relationship between the polymorphism of GCK gene. NIDDM1 （D2S140） gene, FABP2 gene and type 2 diabetes mellitus in Han population of Shandong province. Methods： Short tandem repeat （STR） region polymorphism of GCK gene, NIDDM1 gene and FABP2 gene were analyzed with the polymerase chain reaction and polyacrylamide sequencing gels in 107 subjects with type 2 diabetes mellitus and 105 nodiahetic subjects. All suhjects were biologically unrelated Han population living Shandong without family history. Results： AS allele of GCK gene and B2 allele of D2S140 were associated with type 2 diabetes （RR=15.70, P〈0.01; RR=16.40, P〈0.01）. No difference was found in the frequency of FABP2 alleles between the two groups （P〉0.05）. Logistic regression analysis showed that A5 allele, B2 allele, age, TG, ApoB and LP （a） were associated with type 2 diabetes. Conclusion： Ploymorphic microastellite repeat markers at the GCK gene and the D2S140 gene locus are positively associated with type 2 diabetes in Han population of Shandong province.