Abstract
Objective: To investigate variants of MAOA, SLC2A9 and SLC22A12 associated with higher hyperuricemic risk to develop gout/chronic tophaceous gout. Design: Case-control study. Setting: Hospital- and population -based study from Taiwan and Solomon Islands. Participants: Gout patients (n=374, 157 and 69) and non-gout controls (n=604, 401 and 406) for Taiwan aborigines, Taiwan Han Chinese and Solomon Islanders were recruited. Main outcome measure: MAOA, SLC2A9 and SLC22A12 gene variants were genotyped. Results: In the first study, a synonymous MAOA rs1137070 C allele was associated with the risk of having gout specifying in aborigines (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.11–1.91, P = 4.0× 10-5). MAOA enzyme activity by rs1137070 alleles showed graded associations with hyperuricemia and gout (P for trend=1.53 × 10-6 versus wild-type T allele). Secondly, patients with SLC2A9 rs3733591 Arg265His risk C-allele consistently in both Taiwan Han Chinese and Solomon Islander populations had higher risk for tophaceous gout (OR 2.05, 95% CI 1.11-3.77, P=0.0044; OR 2.08, 95% CI 1.02-4.23, P=0.0184). Thirdly, gout risk was higher concordantly for patients harbouring a common C-allele of SLC22A12 rs475688 in both studied groups (OR 1.98, 95 % CI 1.36-2.88, P=0.0054; OR 1.77, 95% CI 1.10-2.84, P=0.0115, respectively). Moreover, being homozygote at two-locus SLC2A9 rs3733591/ SLC22A12 rs475688 CC/CC-risk score was maximally 14.12-fold in Taiwan Han Chinese (95% CI, 3.57-55.89, P=0.0002) and was 6.98-fold in Solomon Islanders (95% CI 1.02-47.58, P=0.0472) gout risk. Importantly, the interaction term modeled between rs3733591 and rs475688 was significant association with gout in Han (P for interaction=0.0295) but not in Solomon Islanders (P for interaction=0.8622). Conclusion: MAOA gene variants with innate and adaptive immunity may contribute to the development gout in Taiwan aborigines. SLC22A12 and SLC2A9 gene variants were associated with higher hyperuricemic risk to develop gout and to progress tophaceous gout in Han Chinese and replicated in Solomon Islanders.
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