title: Functional polymorphisms of the ABCG2 gene are associated with gout disease in the Chinese Han male population.
abstract: BACKGROUND
  Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population.
  
  
  METHODS
  Peripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K.
  
  
  RESULTS
  For Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77-2.74, p=8.99×10⁻¹³). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49-5.68, p=1.57×10⁻³). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43-0.71, p=2.55×10⁻⁶). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR=2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases.
  
  
  CONCLUSIONS
  The ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.
authors.affiliation: Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China. zzdanqiu@163.com.
authors.forename: Danqiu
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, Renhe Hospital, Baoshan District, Shanghai 200443, China. Liuyunqing@163.com.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Laboratory, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China. pp_dou@163.com.
authors.forename: Xinju
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China. gxiaoye@126.com.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Gu
authors.affiliation: Central Laboratory, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China. fdeduwh@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, China. Luoxinhua@163.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Clinical Laboratory, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, China. zhangjin_jhb@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, China. hejianzou@gmail.com.
authors.forename: Hejian
authors.initials: H
authors.lastname: Zou
authors.affiliation: Central Laboratory, Huashan Hospital, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China. guanming88@yahoo.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002681:China; D005787:Gene Frequency; D005838:Genotype; D006073:Gout / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D044366:Transition Temperature
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins