Abstract
BackgroundTophi 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.MethodsParticipants (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.ResultsCompared 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.ConclusionsVariation in ABCG2 function may play a role in the development of tophaceous disease in some populations with high prevalence of severe gout.
Highlights
Tophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life in people with gout
We have previously reported that a non-synonymous Solute carrier family 2 (SLC2A9) Arg265His variant is associated with tophi in New Zealand Māori with gout [15], and a Taiwanese study has reported an association between ATP-binding cassette sub-family G member 2 (ABCG2) Q141K and tophi in both Han Chinese and Taiwanese aboriginal people with gout [16]
The ABCG2 associations persisted in the Western Polynesian group when including the other ABCG2 variant in the regression model; the age and sex adjusted Odds ratio (OR) for rs2231142 was 1.64 (1.101–2.65), p = 0.045, and for rs10011796 it was 3.60 (1.53–8.44), p = 0.003
Summary
Tophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life in people with gout. Tophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life, and are associated with increased risk of mortality [2,3,4,5]. ABCG2 and SLC2A9, are consistently associated with hyperuricaemia and prevalent gout in many different populations [8,9,10]. He et al Arthritis Research & Therapy (2017) 19:43. The ABCG2 rs2231142 risk allele (Q141K) has population-specific effects in Polynesian people, with a strong association with gout in people of Western Polynesian (Tonga, Samoa, Niue and Tokelau) ancestry, but a weak effect in people of Eastern Polynesian (New Zealand Māori and Cook Island Māori) ancestry [14]
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