新疆维吾尔族人STEAP4基因遗传变异的分布及其与代谢综合征的关联

目的 探讨前列腺六次跨膜上皮抗原4(six transmembrane epithelial antigen of prostate 4,STEAP4)基因多态与维吾尔族人代谢综合征(metabolic syndrome,MetS)的关联.方法 采取以流行病学调查为基础的病例对照研究,选择682例MetS和1228名对照为研究对象.测序筛查维吾尔族MetS患者STEAP4基因功能区的变异,选择代表性变异在维吾尔族自然人群中进行关联分析.结果 维吾尔族人STEAP4基因单核苷酸多态(single nucleotide polymorphism,SNP)的最小等位基因频率不同于中国北京汉族人和欧洲人.rs34741656多态与MetS相关[P=0.034,控制年龄、性别后OR=0.757(95%CI:0.584～0.982)],在对照组,该位点与空腹和餐后2 h血糖水平有关(分别P=0.049,P=0.027).常见单倍型H4(rs8122/rs1981529/rs34741656,G-A-A)可能与MetS有关(permutation P=0.089).结论 STEAP4基因遗传变异可能与维吾尔族人代谢综合征相关.

Abstract：

Objective To investigate the genetic variations of the six transmembrane epithelial antigen of prostate 4 gene (STEAP4)in Chinese Uygur patients with metabolic syndrome (MetS) and to analyze the association of the representative genetic variations of STEAP4 gene with MetS in the population.Methods The sequences of STEAP4 gene functional region (all exons, exon-intron boundaries and the putative promoter region, including the -1 kb 5' and 3'untranslated regions) were amplified and sequenced for patients with MetS. The representative variations were selected based on the function (missense mutation) and linkage disequilibrium (γ2 ＞0. 8) and genotyped with TaqMan-PCR method in 1910 general populations (682 MetS and 1228 non-MetS controls). The subjects were selected from the cross-sectional study of obesity, hypertension, diabetes, dyslipidemia from January to February 2007 among Uygur people,a relatively isolated population with a relatively homogeneous environment, in Hetian area in Xinjiang Uygur Autonomous Region. Results (1) Fourteen novel and six known single nucleotide polymorphisms (SNPs)or mutations, including 2 missense mutations, were identified at the functional region of STEAP4 gene in 96 Uygur patients with MetS. The minor allele frequencies of the SNPs of STEAP4 gene in Uygur population were different from that in European and Chinese Han in Beijing area. (2) The SNP 364G/A (rs34741656,Ala122Thr) was significantly associated with MetS [dominant model P = 0. 034, OR = 0. 757 (95% CI:0. 584-0. 982) adjusted for age and gender], and was associated with fasting blood glucose (FBG) (P =0. 049) and 2-hour postprandial glucose (2HPG) (P = 0. 027) levels in controls. In this SNP, the AA carriers had lower blood glucose levels compared with subjects carrying GG and GT genotypes. (3) The common haplotype H4 (rs8122/rs1981529/rs34741656, G-A-A), may be associated with MetS (permutation P= 0. 089). Conclusion STEAP4 genetic polymorphisms may be associated with MetS risk in Chinese Uygur population.

Genetic variation and association of STEAP4 gene with metabolic syndrome in Chinese Uygur patients

Objective To investigate the genetic variations of the six transmembrane epithelial antigen of prostate 4 gene (STEAP4)in Chinese Uygur patients with metabolic syndrome (MetS) and to analyze the association of the representative genetic variations of STEAP4 gene with MetS in the population.Methods The sequences of STEAP4 gene functional region (all exons, exon-intron boundaries and the putative promoter region, including the -1 kb 5' and 3'untranslated regions) were amplified and sequenced for patients with MetS. The representative variations were selected based on the function (missense mutation) and linkage disequilibrium (γ2 ＞0. 8) and genotyped with TaqMan-PCR method in 1910 general populations (682 MetS and 1228 non-MetS controls). The subjects were selected from the cross-sectional study of obesity, hypertension, diabetes, dyslipidemia from January to February 2007 among Uygur people,a relatively isolated population with a relatively homogeneous environment, in Hetian area in Xinjiang Uygur Autonomous Region. Results (1) Fourteen novel and six known single nucleotide polymorphisms (SNPs)or mutations, including 2 missense mutations, were identified at the functional region of STEAP4 gene in 96 Uygur patients with MetS. The minor allele frequencies of the SNPs of STEAP4 gene in Uygur population were different from that in European and Chinese Han in Beijing area. (2) The SNP 364G/A (rs34741656,Ala122Thr) was significantly associated with MetS [dominant model P = 0. 034, OR = 0. 757 (95% CI:0. 584-0. 982) adjusted for age and gender], and was associated with fasting blood glucose (FBG) (P =0. 049) and 2-hour postprandial glucose (2HPG) (P = 0. 027) levels in controls. In this SNP, the AA carriers had lower blood glucose levels compared with subjects carrying GG and GT genotypes. (3) The common haplotype H4 (rs8122/rs1981529/rs34741656, G-A-A), may be associated with MetS (permutation P= 0. 089). Conclusion STEAP4 genetic polymorphisms may be associated with MetS risk in Chinese Uygur population.