title: Population-specific association between ABCG2 variants and tophaceous disease in people with gout.
abstract: Tophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life in people with gout. The aim of this study was to examine the role of SLC2A9 and ABCG2 variants in tophaceous disease in people with gout.
  
  
  
  Participants (n = 1778) with gout fulfilling the 1977 American Rheumatism Association (ARA) classification criteria, who were recruited from primary and secondary care, attended a detailed study visit. The presence of palpable tophi was recorded. SLC2A9 rs11942223, ABCG2 rs2231142 and ABCG2 rs10011796 were genotyped. Data were analysed according to tophus status.
  
  
  
  Compared to participants without tophi, those with tophi were older, had longer disease duration and higher serum creatinine, and were more likely to be of Māori or Pacific (Polynesian) ancestry. SLC2A9 rs11942223 was not associated with tophi. However, the risk alleles for both ABCG2 single nucleotide polymorphisms (SNPs) were present more frequently in those with tophi (OR (95% CI) 1.24 (1.02-1.51) for rs2231142 and 1.33 (1.01-1.74) for rs10011796, p < 0.05 for both). The effect of rs2231142 was limited to participants of Māori or Pacific ancestry (OR 1.50 (1.14-1.99), p = 0.004), with a significant effect observed in those of Western Polynesian ancestry only (OR 1.71 (1.07-2.72), p = 0.017). The rs10011796 risk allele was strongly associated with tophi in the Western Polynesian group (OR 3.76 (1.61-8.77), p = 0.002), but not in the Eastern Polynesian group (OR 0.87 (0.52-1.46), p = 0.60) nor in the non-Polynesian group (OR 1.16 (0.81-1.66), p = 0.32). The ABCG2 associations persisted in the Western Polynesian group after adjusting for serum urate, creatinine, and disease duration, and when including both ABCG2 variants in the regression models.
  
  
  
  Variation in ABCG2 function may play a role in the development of tophaceous disease in some populations with high prevalence of severe gout.
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand.
authors.forename: Wendy
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Amanda
authors.initials: A
authors.lastname: Phipps-Green
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006073:Gout / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D051246:Glucose Transport Proteins, Facilitative; D009363:Neoplasm Proteins; C411811:SLC2A9 protein, human
keywords: ABCG2; Gout; Tophus genetics