Variation in the Uric Acid Transporter Gene SLC2A9 and Its Association with AAO of Parkinson's Disease
Variation in the Uric Acid Transporter Gene SLC2A9 and Its Association with AAO of Parkinson's Disease
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DOI：
10.1007/s12031-010-9409-y
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发表时间：
2011-03-01
影响因子：
3.1
通讯作者：
Pramstaller, Peter P.
中科院分区：
文献类型：
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作者：
Facheris, Maurizio F.;Hicks, Andrew A.;Pramstaller, Peter P.
根据观察到的高尿酸血症与帕金森病（PD）风险之间的负相关关系，尿酸的天然抗氧化活性已被认为发挥保护作用。SLC2A9已被证明是所有尿酸转运蛋白中最有效的，SLC2A9变体已被证明影响循环尿酸水平。通过这项研究，我们旨在测试SLC2A9多态性与PD发病年龄（AAO）之间的关系。SLC2A9中的rs733175、rs737267、rs1014290和rs6449213变体在来自三个欧洲中心的664名PD患者中进行了基因分型。每个中心使用线性回归模型对其他snp的性别和基因型进行调整，并假设加性遗传模型，估计每个多态性对AAO的影响。各中心的结果采用反方差加权固定效应荟萃分析相结合。rs1014290的次要等位基因，先前被证明与较低的血清尿酸水平相关，被发现与较低的PD AAO相关（汇总估计-4.56年；95% CI -8.13, -1.00; p = 0.012）。在对多个比较进行调整后，这种关联仍然显著，并且在各中心之间高度一致（异质性，I(2) 0%）。没有观察到性别差异。我们的研究表明SLC2A9基因变异影响帕金森病的发病年龄。
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.