汉族人群脂联素基因＋712A／G和＋349A／G多态性与2型糖尿病的关联性研究

Association of +712A/G and +349A/G polymorphisms in the adiponectin gene with type 2 diabetes mellitus in Han population

目的探讨中国四川地区汉族人群脂联素基因(APM1)单核苷酸多态性(SNP)和2型糖尿病(T2DM)及其血脂水平的关联性。方法研究对象819例,包括对照组405例,T2DM组414例。测定血脂水平和腰臀比值(WHR);稳态模型(HOMA)计算胰岛素抵抗(IR)指数。PCR-RFLP和基因测序方法鉴定2号内含子(IVS2)+712A/G和+349A/G多态性。结果APM1基因IVS2+712A/G位点GG基因型与(AA+AG)基因型在对照组与T2DM组内的分布差异有统计学意义(P<0.05),T2DM组内GG基因型患者血浆总胆固醇(TC)和低密度脂蛋白(LDL)值均高于(AA+AG)基因型(P<0.05);IVS2+349A/G位点各基因型及等位基因频率在对照组与T2DM组内的分布差异无统计学意义(P>0.05),两组内各基因型间血脂水平差异无统计学意义(P>0.05);IVS2+712A/G与IVS2+349A/G存在强的连锁不平衡(D′=0.893)。结论APM1基因IVS2+712A/G位点GG基因型与T2DM及其血浆TC和LDL水平升高关联,A→G多态性提高了T2DM合并血脂代谢紊乱的风险性;IVS2+349A/G与+712A/G紧密连锁。

Objective To investigate the association of adiponectin gene （APM1） polymorphism with type 2 diabetes mellitus （T2DM） and serum lipid levels. Methods APM1 gene IVS2 ＋ 712A/G and IVS2 ＋ 349A/G polymorphisms were identified by means of PCR-RFLP among 819 subjects, including 414 T2DM cases and 405 controls. Serum lipid levels were detected, the waist-to-hip ratios （WHR） were calculated and the homeostasis model assessment （HOMA） was used to measure insulin resistance（IR）. Data were analyzed with SPSS13.0 software. Results The distribution frequencies of the alleles and genotypes were in agreement with the Hardy Weinberg equilibrium. No significantly different was found in allele frequencies and genotype distributions of APM1 gene IVS2 ＋ 712A/G polymorphism between T2DM patients and control subjects （P 〉 0.05）. However, compared with GG genotype, the distribution of AA ＋ AG genotype was significantly different between T2 D M patients and control subjects （χ^2 = 4.416, P 〈 0.05, OR = 1. 445,95 % CI = 1. 024 - 2. 038 ）. Patients with GG genotypes had higher levels of TC and LDL-C （ F1 = 8. 400, P1 = 0. 004 ; F2 = 8. 486, P2 = 0. 004 ） than patients with AA ＋ AG genotype. No significant difference was found in allele frequencies and genotype distributions of APM1 gene IVS2 ＋ 349A/G polymorphism between T2DM patients and control subjects （ P 〉 0. 05 ）. Further study on serum lipid levels indicated that there were no significant differences in different genotypes in each group. APM1 gene IVS2 ＋712A/G and IVS2 ＋ 349A/G polymorphisms were displayed strong linkage disequilibrium （D′ = 0. 893 ）. Conclusions The GG genotype of APM1 gene IVS2 ＋ 712 site may be associated with the occurrence of T2DM and increase the genetic risk of developing T2DM together with lipids disorder. APM1 gene IVS2 ＋ 349A/G polymorphism is not associated with T2DM but tightly linked with IVS2 ＋ 712A/G.