Variation in the uric acid transporter gene SLC2A9 and its association with AAO of Parkinson's disease

Abstract

Based on the observed inverse association between hyperuricemia and Parkinson's disease (PD) risk, the natural antioxidant activity of uric acid has been suggested to play a protective role. SLC2A9 has been indicated as the most effective of all uric acid transporters, and SLC2A9 variants have been shown to influence circulating uric acid levels. With this study, we aimed to test the association between such SLC2A9 polymorphisms and age at onset (AAO) of PD. Variants rs733175, rs737267, rs1014290, and rs6449213 within SLC2A9 were genotyped in 664 PD individuals from three European centers. The effect of each polymorphism on AAO was estimated within each center using a linear regression model adjusted for gender and genotype at the other SNPs and assuming an additive genetic model. Results across centers were combined using inverse-variance weighted fixed-effect meta-analysis. The minor allele of rs1014290, previously shown to be associated with lower serum uric acid levels, was found to be associated with a lower AAO of PD (pooled estimate -4.56 years; 95% CI -8.13, -1.00; p=0.012). The association remained significant after adjustment for multiple comparisons and was highly consistent across centers (heterogeneity, I (2) 0%). No gender differences were observed. Our study suggests that SLC2A9 genetic variants influence age of onset of Parkinson's disease.