Abstract
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.
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Acknowledgments
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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Tu, HP., Ko, A.MS., Wang, SJ. et al. Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines. Hum Genet 127, 223–229 (2010). https://doi.org/10.1007/s00439-009-0765-z
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DOI: https://doi.org/10.1007/s00439-009-0765-z