2型糖尿病的分子病因学研究

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、NIDDM1（D2S140）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A5及D2S140等位基因B2与2型糖尿病呈正相关（P＜0.01）;GCK等位基因A1、A3及D2S140等位基因B6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A5及B2、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A3及B6呈显著负相关.结论GCK基因、NIDDM1（D2S140）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.

Study of molecule etiology in patients with type 2 diabetes mellitus

Objective: To determine the relationship between the polymorphism of GCK gene,NIDDM_1(D2S140) gene,FABP_2 gene and type 2 diabetes mellitus inHanpopulation of Shandong province.Methods: Short tandem repeat(STR) region polymorphism of GCK gene,NIDDM_1 gene and FABP_2 gene were analyzed with the polymerasechain reaction and polyacrylamide sequencing gels in 107 subjects with type 2 diabetes mellitus and 105 nodiabetic subjects.All subjects were biologically unrelated Han population living Shandong without family history.Results: A5 alleleof 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 FABP_2alleles between the two groups (P>0.05).Logistic regression analysis showedthat A5 allele,B2 allele,age,TG,ApoB and LP(a) were associated with type 2diabetes.Conclusion: Ploymorphic microastellite repeat markers at the GCK gene andthe D2S140 gene locus are positively associated with type 2 diabetes in Han population of Shandong province.