Gender Specific Effect of Brain-Derived Neurotrophic Factor (BDNF) Gene SNP G196A on Susceptibility to Alzheimer’s Disease: A Meta- Analysis

Abstract

Alzheimer’s Disease (AD) is one of the most common age-associated neurodegenerative disorders worldwide. The pathogenesis of AD has been found to be associated to genetic polymorphisms in several case-control and cohort studies for the BDNF -196G>A (rs6265) gene polymorphism but have yielded inconsistent results. In this study, PubMed, EMBASE, and Science Direct web-databases were searched for relevant reports, showing association of BDNF -196G>A gene with AD risk. A total of 19 reports involving 5238 AD cases and 5492 controls were included. Significant associations in five genetic models, i.e. allelic (A vs G: p = 0.001; OR = 1.139, 95% CI = 1.051 to 1.233); homozygous (AA vs GG: p = 0.016; OR = 1.264, 95% CI = 1.044 to 1.530); heterozygous (AG vs GG: p = 0.015; OR = 1.146, 95% CI = 1.027 to 1.279) ; and dominant (AA+AG vs GG: p = 0.003; OR = 1.175, 95% CI = 1.058 to 1.305) were found in overall analysis in case of female subjects but not in male subjects. The results suggest that BDNF -196G>A gene polymorphism significantly contributes to AD susceptibility in females. Trial Sequential Analysis (TSA) was also conducted and results showed that the conclusions in this meta-analysis are robust.