STEAP4基因多态性与维吾尔族人胰岛素抵抗的相关性

摘要

目的 研究前列腺六次跨膜上皮抗原4(STEAP4)基因多态性与维吾尔族人胰岛素抵抗的关系.方法 研究对象来自新疆和田地区2127例维吾尔族人肥胖等代谢性疾病的横断面调查研究,胰岛素抵抗病例组669例[胰岛素抵抗指数(HOMA-IR)≥2.365%],正常对照组664例(HOMA-IR≤1.335%).首先对50例胰岛素抵抗患者(HOMA-IR≥2.3)STEAP4基因的功能区进行测序,根据连锁不平衡(r2＞0.8)和最小等位基因频率＞5%的原则选择代表性变异在自然人群中行病例对照关联研究.结果 STEAP4基因测序共发现16个变异,其中新发现10个.在关联分析的3个变异中,rs8122(P/Pc=0.004/0.012)和rs1981529(P/Pc=0.015/0.045)与维吾尔族人的胰岛素抵抗表型关联.多元线性回归分析结果显示,rs8122 3种基因型间(GG＞GA＞AA)的腰围(P/Pc=0.032/0.256)、体重指数(BMI)(P/Pc=0.004/0.032)、HOMA-IR(P/Pc=0.010/0.08)、空腹胰岛素(P/Pc=0.023/0.184)及rs1981529 3种基因型间(AA＞AG＞GG)的腰围(P/Pc=0.005/0.040)、BMI(P/Pc=0.002/0.016)水平均有逐渐减小趋势.胰岛素抵抗病例组单倍型1(rs8122 G-rs1981529 A-rs34741656 G)的频率明显高于对照组(P=0.021).结论 STEAP4基因多态性与新疆维吾尔族人的肥胖相关胰岛素抵抗关联.%Objective To explore the relationship between six-transmembrane epithelial antigen of prostate 4 (STEAP4) genetic polymorphisms and insulin resistance (IR) in Uygur Chinese general population.Methods In this cross-sectional study on the metabolic diseases ( e. g. obesity) among Uygur Chinese in He tian, Xinjiang, China, from January to February 2007, 2127 Uygur individuals were enrolled. The sample size for IR subjects [homeostasis model assessment for insulin resistance (HOMA-IR) ≥2. 365％ ] was 669,whereas that for non-IR controls was 664 (HOMA-IR ≤ 1.335％ ). STEAP4 gene was sequenced in 50 Uygur Chinese individuals with IR (HOMA-IR≥2.3). The representative variations were selected from the popula tion based on a r2 cutoff of 0.8 and a minor allele frequency of ＞ 5 ％ for case-control study. Results Totally 16 variations including 10 novel variations (no reported in dbSNP) were identified in 50 Uygur individuals with IR. 7414 G/A (rs8122) (P/Pc=0. 004/0. 012) and 224A/G (rs1981529, Gly75Asp) (P/Pc =0. 015/0. 045 ) variations were significantly correlated with IR phenotype in Uygur subjects. As shown by multiple linear regression analysis, the mean values of waist circumference (WC) ( P/Pc =O. 032/0. 256), body mass index (BMI) ( P/Pc = O. 004/0. 032), HOMA-IR ( P/Pc = O. 010/0.08 ), and fasting insulin ( P/Pc =0. 023/0. 184) among A (protection) allele carriers of rs8122 and the mean values of WC ( P/Pc =O. 005/0. 040) and BMI (P/Pc = O. 002/0. 016) among G (protection) allele carriers of rs1981529 gradually declined. Haplotype 1 (rs8122 G- rs1981529 A- rs34741656 G) was significantly associated with a higher prevalence of IR (Permutation P =0. 021 ). Conclusion STEAP4 genetic variations are likely to be associated with obesity-related insulin resistance in Uygur Chinese general population.