Variations of Six Transmembrane Epithelial Antigen of Prostate 4 (STEAP4) Gene Are Associated with Metabolic Syndrome in a Female Uygur General Population

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• 作者：Li Nanfang ; Guo Yanying ; Wang Hongmei ; Yan Zhitao ; Zhang Juhong ; Zhou Ling ; Luo Wenli
• 关键词：Genetic association study ; Metabolic syndrome ; Uygur ; STEAP4
• 刊名：Archives of Medical Research
• 出版年：2010
• 出版时间：August 2010
• 年：2010
• 卷：41
• 期：6
• 页码：449-456
• 全文大小：127 K

文摘

Background and Aims

Metabolic syndrome (MetS) is linked with visceral obesity and is associated with a clustering of abnormalities (including impaired glucose tolerance, insulin resistance, dyslipidemia and hypertension). Six transmembrane epithelial antigen of prostate 4 (STEAP4) was associated with human obesity. STEAP4 gene represents a strong biological and positional candidate for a susceptibility factor for MetS. Uygur Chinese is a relatively isolated population with a relatively homogeneous environment and a high prevalence of MetS. We undertook this study to investigate the relationship between STEAP4 gene variations and MetS in a Uygur general population.

Methods

The functional regions of STEAP4 gene were sequenced in Uygur patients with MetS. Four representative variations, rs1981529, rs34741656, rs8122 and 6031T/G (unsuccessfully genotyped), selected with a r² cutoff of 0.8 and minor allele frequency of >5 % , were genotyped in 858 MetS and 687 non-MetS controls.

Results

Fourteen novel and six known single nucleotide polymorphisms (SNPs) including 2 nonsynonymous SNPs in the STEAP4 gene were identified. SNPs rs8122 and rs1981529 were significantly associated with MetS phenotype in females [additive p = 0.032 and p = 0.011; ORs (95 % CI) adjusted for age 0.772 (0.625–0.954) and 0.740 (0.582–0.941), respectively]. Two common haplotypes 1 (rs8122/rs1981529/rs34741656, G-A-G) and 2 (A-G-G) had significantly higher (permutation p = 0.044) and lower (permutation p = 0.009) frequency in MetS than that in controls in females. Multiple linear regression analysis revealed a significant association of the SNPs rs8122 and rs1981529 with HDL-c level in MetS cases (p = 0.001 and 0.024) and in a combined sample (p = 0.004 and 0.009).

Conclusions

STEAP4 genetic variations are likely to be associated with metabolic syndrome in a female Uygur general population.