Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines
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Taiwanese aborigines have a high prevalence of hyperuricemia and gout. Uric acid levels and urate excretion have correlated with dopamine-induced glomerular filtration response. MAOs represent one of the major renal dopamine metabolic pathways. We aimed to identify the monoamine oxidase A (MAOA, Xp11.3) gene variants and MAO-A enzyme activity associated with gout risk. This study was to investigate the association between gout and the MAOA single-nucleotide polymorphisms (SNPs) rs5953210, rs2283725, and rs1137070 as well as between gout and the COMT SNPs rs4680 Val158Met for 374 gout cases and 604 controls. MAO-A activity was also measured. All three MAOA SNPs were significantly associated with gout. A synonymous MAOA SNP, rs1137070 Asp470Asp, located in exon 14, was associated with the risk of having gout (P = 4.0 × 10−5, adjusted odds ratio 1.46, 95% confidence intervals [CI]: 1.11–1.91). We also showed that, when compared to individuals with the MAOA GAT haplotype, carriers of the AGC haplotype had a 1.67-fold (95% CI: 1.28–2.17) higher risk of gout. Moreover, we found that MAOA enzyme activity correlated positively with hyperuricemia and gout (P for trend = 2.00 × 10−3 vs. normal control). We also found that MAOA enzyme activity by rs1137070 allele was associated with hyperuricemia and gout (P for trend = 1.53 × 10−6 vs. wild-type allele). Thus, our results show that some MAOA alleles, which have a higher enzyme activity, predispose to the development of gout.
KeywordsGout Hyperuricemia Uric Acid Level Serum Uric Acid Level Proximal Tubule Cell
We thank the medical staffs and primary care doctors at Jianshih and Wufong health center for the precise clinical phenotypes. We thank the study staff (Chun-Lan Hsu, Yu Tai and Chih-Shan Liu) from Division of Environmental Health and Occupational Medicine, National Health Research Institutes for data handling. This study was supported by grants from the National Health Research Institutes (NHRI-98A1-PDCO-0307101), Center of Excellence for Environmental Medicine, Kaohsiung Medical University (KMU-EM-98-1-1), and the National Science Council (NSC97-2314-B-037-007 and NSC97-3112-B-400-001).
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