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Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population

  
@article{APS4485,
	author = {Xue Sun and Feng Jiang and Rong Zhang and Shan-shan Tang and Miao Chen and Dan-feng Peng and Jing Yan and Tao Wang and Shi-yun Wang and Yu-qian Bao and Cheng Hu and Wei-ping Jia},
	title = {Serum uric acid levels are associated with polymorphisms in the  SLC2A9 ,  SF1 , and  GCKR  genes in a Chinese population},
	journal = {Acta Pharmacologica Sinica},
	volume = {35},
	number = {11},
	year = {2016},
	keywords = {},
	abstract = {Xue SUN1, #, Feng JIANG1, #, Rong ZHANG1, Shan-shan TANG1, Miao CHEN1, Dan-feng PENG1, Jing YAN1, Tao WANG1, Shi-yun WANG1, Yu-qian BAO1, Cheng HU1, 2, *, Wei-ping JIA1, *
1Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai 201400, China
 
Aim: Genome-wide association studies have identified several novel loci associated with serum uric acid concentrations in individuals of European descent. In the current study, we aimed to evaluate the associations between these loci and serum uric acid concentrations in a Chinese population.
Methods: Fourteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped in 2329 Chinese subjects in Shanghai. Serum biochemical parameters including uric acid concentrations were determined. All the variants were analyzed for gender differences since uric acid metabolism differed between genders.

Results: In males after adjustments for age and BMI, GCKR rs780094, SLC2A9 rs11722228 and SF1 rs606458 were associated with the uric acid concentrations, which were statistically significant (P=0.016, 0.001 and 0.03, respectively), whereas SLC2A9 rs3775948 was marginally associated with the uric acid concentrations (P=0.071). In females, SLC22A12 rs506338 was also marginally associated with the uric acid concentrations (P=0.057). The meta-analysis for combined data from both males and females revealed that rs3775948 and rs606458 were associated with the uric acid concentrations (P=0.036 and 0.043, respectively). Furthermore, the gender significantly affected the association of rs11722228 with serum uric acid levels (P=0.012).

Conclusion: The SLC2A9 rs11722228, SF1 rs606458 and GCKR rs780094 variants modulate uric acid concentrations in Chinese males, while SF1 rs606458 and SLC2A9 rs3775948 are associated with the uric acid concentrations in both Chinese males and females.

 
Keywords: uric acid; gout; single nucleotide polymorphisms; SLC2A9; SF1; GCKR; genome-wide association; Chinese
 
We thank all participants of this research. We thank the nursing and medical staff at the Shanghai Clinical Center for Diabetes for their dedication to this study. We acknowledge grants from National Natural Science Foundation of China (No 81322010), Excellent Young Medical Expert of Shanghai (No XYQ2011041), the Shanghai Rising Star Program (No 12QH1401700), the Shanghai Talent Development Grant (No 2012041) and the National Program for Support of Top-notch Young Professionals.
# These authors contributed equally to this work. 
* To whom correspondence should be addressed. 
E-mail alfredhc@sjtu.edu.cn (Cheng HU); wpjia@sjtu.edu.cn (Wei-ping JIA) 
Received 2014-05-22     Accepted 2014-07-31},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4485}
}