Variations of six transmembrane epithelial antigen of prostate 4 (STEAP4) gene are associated with metabolic syndrome in a female Uygur general population.
OBJECTIVE
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.
Department of Hypertension, People's Hospital of Xinjiang Uygur Autonomous Region, The Center of Diagnosis, Treatment and Research of Hypertension in Xinjiang, Urumqi, Xinjiang, China. lnanfang2009@hotmail.com
Li
L
Nanfang
Guo
G
Yanying
Wang
W
Hongmei
Yan
Y
Zhitao
Zhang
Z
Juhong
Zhou
Z
Ling
Luo
L
Wenli
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
D008565:Membrane Proteins; D010088:Oxidoreductases; C503310:STEAP4 protein, human