rs3851179 Polymorphism at 5 ′ to the PICALM Gene is Associated with Alzheimer and Parkinson Diseases in Brazilian Population

AbstractAlzheimer ’s (AD) and Parkinson’s diseases (PD) share clinical and pathological features, suggesting that they could have common pathogenic mechanisms, as well as overlapping genetic modifiers. Here, we performed a case–control study in a Brazilian population to clarify whether the risk of AD and PD mig ht be influenced by shared polymorphisms atPICALM (rs3851179),CR1 (rs6656401) andCLU (rs11136000) genes, which were previously identified as AD risk factors by genome-wide association studies. For this purpose, 174 late-onset AD patients, 166 PD patients and 176 matched controls were genotyped using TaqMan® assays. The results revealed that there were significant differences in genotype and allele frequencies for the SNPPICALM rs3851179 between AD/PD cases and controls, but none forCR1 rs6656401 andCLU rs11136000 intronic polymorphisms. After stratification byAPOEε4 status, the protective effect of thePICALM rs3851179 A allele in AD cases remains evident only inAPOEε4 (−) carriers, suggesting that theAPOEε4 risky allele weakens its protective effect in theAPOEε4 (+) subgroup. More genetic studies using large-sized and well-defined matched samples of AD and PD patients from mixed populations as well as functional correlation analysis are urgently needed to clarify the role of rs3851179 in the AD/PD risk. An understanding of the contribution of rs3851179 to the development of AD and PD could provide new targets for the development of novel therapies.
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research