A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population

BMC Medical Genomics

Meian He³  Tangchun Wu³  Dongxin Lin⁶  Frank B Hu⁴  Dongfeng Li⁷  Mingjian Lang⁷  Xinwen Min⁷  Jiang Zhu⁷  Tian Wang³  Xiao Zhang³  Die Hu³  Lei Guan³  Yingying Feng³  Qifei Deng³  Suli Huang³  Gaokun Qiu³  Jun Li³  Xiayun Dai³  Jing Yuan³  Xiaomin Zhang³  Huan Guo³  Li Zhou¹  Lixuan Gui³  Yunfeng He³  Xiaobo Yang²  Handong Yang⁷  Chen Wu⁶  Zengnan Mo⁵  Binyao Yang³ 

[1] Department of Epidemiology, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China;Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China;Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei, China;Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston 02115, MA, USA;Institute of Urology and Nephrology, First Affiliated Hospital & Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China;State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China;Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan 442008, Hubei, China

关键词: Gene-environment interaction;    Ethnic differences;    Serum uric acid;    Genome-wide association study;   

Others  :  797113
DOI  :  10.1186/1755-8794-7-10

 received in 2013-02-25, accepted in 2014-02-05,  发布年份 2014

【 摘 要 】

Background

Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited.

Methods

A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort.

Results

Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10^-31) and ABCG2 (rs2231142, combined P = 3.34 × 10^-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10^-2 and 2.0 × 10^-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females.

Conclusions

Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender.

【 授权许可】

   
2014 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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