Search

GOLPH2 gene SNP variants Rs10868366 and Rs7019241 were reported to decrease the risk of Alzheimer's disease in a recent Whole Genome Association Study. We have investigated these genetic variants in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP markers. We found no evidence of association between GOLPH2 markers and susceptibility to Alzheimer's disease in our series. We concluded that GOLPH2 gene does not contribute to risk of disease in this study sample. [ABSTRACT FROM AUTHOR]

Abstract: The relationships between genome wide association study-identified and replicated genetic variants associated with Alzheimer''s disease (AD) risk and disease progression or therapeutic responses in AD patients are almost unexplored. Seven hundred and one AD patients with at least 3 different cognitive evaluations and genotypic information for APOE and 6 genome wide association study-significant single-nucleotide polymorphisms were selected for this study. Mean differences in Global Deterioration Score and Mini Mental State Examination (MMSE) were evaluated using nonparametric tests, general linear model and mixed models for repeated measurements. Each chart was also reviewed for evidence of treatment with any cholinesterase inhibitor, memantine, or both. Relationships between therapeutic protocols, genetic markers, and progression were explored using stratified analysis looking for specific effects on progression in each therapeutic category separately. Neither calculation rendered a Bonferroni-corrected statistically significant difference in any genetic marker. Mixed model results suggested differences in the average point in MMSE test for patients carrying PICALM GA or AA genotype compared with GG carriers at the end of the follow-up (MMSE mean difference = −0.57; 95% confidence interval, −1.145 to 0.009; p = 0.047). This observation remained unaltered after covariate adjustments although it did not achieve predefined multiple testing significance threshold. The PICALM single-nucleotide polymorphism also displayed a significant effect protecting against rapid progression during pharmacogenetic assays although its observed effect displayed heterogeneity among AD therapeutic protocols (p = 0.039). None of the studied genetic markers were convincingly linked to AD progression or drug response. However, by using different statistical approaches, the PICALM rs3851179 marker displayed consistent but weak effects on disease progression phenotypes. [Copyright &y& Elsevier]