Alzheimer's Disease-Associated SNP rs708727 in SLC41A1 May Increase Risk for Parkinson's Disease: Report from Enlarged Slovak Study

SLC41A1 (A1) SNPs rs11240569 and rs823156 are associated with altered risk for Parkinson's disease (PD), predominantly in Asian populations, and rs708727 has been linked to Alzheimer's disease (AD). In this study, we have examined a potential association of the three aforementioned SNPs and of rs9438393, rs56152218, and rs61822602 (all three lying in the A1 promoter region) with PD in the Slovak population. Out of the six tested SNPs, we have identified only rs708727 as being associated with an increased risk for PD onset in Slovaks. The minor allele (A) in rs708727 is associated with PD in dominant and completely over-dominant genetic models (ORD = 1.36 (1.05-1.77), p = 0.02, and ORCOD = 1.34 (1.04-1.72), p = 0.02). Furthermore, the genotypic triplet GG((rs708727)) + AG((rs823156)) + CC(rs61822602) might be clinically relevant despite showing a medium (h >= 0.5) size difference (h = 0.522) between the PD and the control populations. RandomForest modeling has identified the power of the tested SNPs for discriminating between PD-patients and the controls to be essentially zero. The identified association of rs708727 with PD in the Slovak population leads us to hypothesize that this A1 polymorphism, which is involved in the epigenetic regulation of the expression of the AD-linked gene PM20D1, is also involved in the pathoetiology of PD (or universally in neurodegeneration) through the same or similar mechanism as in AD.