单基因变异与中国北方汉族2型糖尿病遗传易感性研究  

Variants in KCNQ1,AP3S1,MAN2A1 and ALDH7A1 and the risk of type 2 diabetes in the Chinese northern Han population

作　　者：周建博[1] 信中[1] 冯建萍[1] 杨金奎[1] 

机构地区：[1]首都医科大学附属北京同仁医院内分泌科,北京100730

出　　处：《首都医科大学学报》2012年第4期468-471,共4页Journal of Capital Medical University

基　　金：国家自然科学基金(30671001)~~

摘　　要：目的在东亚和西非人群中分别进行的全基因组关联研究筛查出KCNQ1基因的rs2237892,AP3S1基因的rs3756555,MAN2A1基因的rs2015698为2型糖尿病易感位点,ALDH7A1基因rs2306617则与肥胖存在关联,而这些位点的作用尚未在中国北方汉族人群中进行探讨,本研究的目的是在中国北方汉族2型糖尿病患者中对这些可能的易感位点进行复制研究。方法应用基质辅助激光解吸电离飞行时间质谱对KCNQ1基因的rs2237892,AP3S1基因的rs3756555,MAN2A1基因的rs2015698,ALDH7A1基因的rs2306617在无血缘关系的537名2型糖尿病患者和510名对照者中进行基因分型。结果 rs2237892和rs3756555位点的C等位基因显著增加2型糖尿病遗传易感性(P=0.002,P=0.003)。该显著性关联在调整年龄、性别和体质量指数(body mass index,BMI)后仍然存在(OR=1.51,95%CI:1.17～1.95,P=0.002;OR=1.48,95%CI:1.14～1.92,P=0.003)。未能发现rs2015698和rs2306617与2型糖尿病存在关联。通过对对照人群研究发现,调整年龄、性别和BMI后,rs2237892位点CC基因型空腹血糖显著高于其他2基因型(P=0.020);与其他两基因型相比,rs3756555位点CC基因型BMI略有降低(P=0.050)。结论 KCNQ1基因和AP3S1基因遗传变异与中国北方汉族2型糖尿病遗传易感性相关。The recent studies have explored several novel type 2 diabetes susceptibility variants in KCNQ1 （rs2237892）, AP3S1 （rs3756555） , MAN2A1 （rs2015698） and ALDH7A1 （rs2306617） genes. This study aimed to evaluate the contribution of these variants in the four genes to predisposition of type 2 diabetes in the Chinese northern Han population. Methods Four candidate single nueleotide polymorphisms, rs2237892, rs2306617, rs2015698 and rs3756555 were selected, and genotyped them in 537 unrelated individuals with type 2 diabetes and 510 normal controls. Results The C risk allele in rs2237892 and rs3756555 conferred a significantly increased susceptibility to type 2 diabetes（P=0. 002, P = 0. 003 ）. The significant association remains after adjusting the age, sex and BMI（ OR= 1.51, 95% CI： 1.17 - 1.95, P= 0. 002 ; OR = 1.48, 95% CI： 1. 14 - 1.92, P = 0. 003 ）. No association was observed in recessive genetic models for rs2015698 and rs2306617. Further investigation in the control subjects showed that fasting plasma glucose was significantly higher for the individuals with CC genotype of rs2237892 than for those with the other two genotypes after adjusting for age, sex and BMI（P=0.020）. The SNP of rs3756555 was marginally associated with BMI in recessive model（P=0.050）. Conclusion In this study the effects of KCNQ1 and AP3S1 variants on the susceptibility to type 2 diabetes in the Chinese northern Han population were confirmed.

关 键 词：2型糖尿病 KCNQ1 AP3S1 空腹血糖 

分 类 号：R587.1[医药卫生—内分泌]