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）≥2.3 65%］，正常对照组664例（HOMA-IR≤1.3 35%）。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 Hetian, 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) ≥2.3 65%］ 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 population 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=0.032/0.256), body mass index (BMI) (P/Pc=0.004/0.032), HOMA-IR (P/Pc=0.010/0.08), and fasting insulin (P/Pc=0.023/0.184) among A (protection) allele carriers of rs8122 and the mean values of WC (P/Pc=0.005/0.040) and BMI (P/Pc=0.002/0.016) 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.
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