Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines.

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 x 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 x 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 x 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.

• Authors: Hung-Pin Tu, Albert Min-Shan Ko, Shu-Jung Wang, Chien-Hung Lee, Rod A Lea, Shang-Lun Chiang, Hung-Che Chiang, Tsu-Nai Wang, Meng-Chuan Huang, Tsan-Teng Ou, Gau-Tyan Lin, Ying-Chin Ko
• Journal: Human genetics (Hum Genet) Vol. 127 Issue 2 Pg. 223-9 (Feb 2010) ISSN: 1432-1203 [Electronic] Germany
• PMID: 19915868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Uric Acid
• Monoamine Oxidase

Topics

• Adult
• Aged
• Alleles
• Asian People (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Gout (enzymology, ethnology, genetics)
• Haplotypes
• Humans
• Linkage Disequilibrium
• Male
• Middle Aged
• Monoamine Oxidase (genetics, metabolism)
• Polymorphism, Single Nucleotide
• Risk Factors
• Taiwan
• Uric Acid (blood)