title: Effects of multiple genetic loci on the pathogenesis from serum urate to gout.
abstract: Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (PFDR< 0.05) in the Chinese population for the first time. ABCG2 and a novel gene, SLC17A4, contributed to the development of gout from hyperuricemia (OR = 1.56, PFDR= 3.68E-09; OR = 1.27, PFDR= 0.013, respectively). Also, HNF4G is a novel gene associated with susceptibility to gout (OR = 1.28, PFDR= 1.08E-03). In addition, A1CF and TRIM46 were identified as associated with gout in the Chinese population for the first time (PFDR< 0.05). The present study systematically determined genetic effects on the progression from elevated serum urate to gout and suggests that urate-associated genes functioning as urate transporters may play a specific role in the pathogenesis of gout. Furthermore, two novel gout-associated genes (HNF4G and SLC17A4) were identified.
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Rheumatology and Immunology, Changhai Hospital, Shanghai, China.
authors.forename: Dongbao
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Division of Rheumatology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Chengde
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Rheumatology, Taixing People's Hospital, Jiangsu Province, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: He
authors.affiliation: Division of Rheumatology, Taizhou People's Hospital, Jiangsu Province, China.
authors.forename: Hengdong
authors.initials: H
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Rheumatology and Immunology, Changhai Hospital, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Rheumatology and Immunology, Changhai Hospital, Shanghai, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.|Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Jiangwan Campus, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.|Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006073:Gout / Q000097:blood* / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D014527:Uric Acid