The association of 5HT2A and 5HTTLPR polymorphisms with Alzheimer’s disease susceptibility: a meta-analysis with 6945 subjects

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Relationships of 5HT2A and 5HTTLPR polymorphisms and AD risk have been widely investigated previously, whereas results derived from these studies were inconclusive and controversial. The aim of this study was to investigate the association of the 5-HT2A and 5HTTLPR polymorphisms and AD using a meta-analysis of existing literatures. Studies were collected using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess associations. As a result, a total of 7 publications for 5-HT2A T102C and 16 publications for 5HTTLPR (L/S) comprised 3255 cases and 3690 controls fulfilled the inclusion criteria. Significant association was covered between allelic and recessive models of 5-HT2A T102C and AD (allelic model: p = 0.003, OR [95% CI] = 1.23 [1.07, 1.40]; recessive model: p = 0.03, OR [95% CI] = 1.28 [1.02, 1.59]). Subsequently, we conducted subgroup analysis for 5-HT2A T102C polymorphism based on ethnicities and APOE ε4, and identified a significantly increased risk for the allelic and dominant models of 5-HT2A T102C and AD in Asian subgroup (allelic model: p = 0.002, OR [95% CI] = 1.42 [1.14, 1.78]; dominant model: p = 0.02, OR [95% CI] = 1.60 [1.09, 2.35]) and subgroup without APOE ε4 (allelic model: p = 0.02, OR [95% CI] = 1.44 [1.05, 1.99]; dominant model: p = 0.0008, OR [95% CI] = 2.49 [1.46, 4.25]). Nevertheless, the pooled analyses suggested no significant association between allelic, dominant, and recessive models of 5HTTLPR (L/S) and AD (p > 0.05). In conclusion, our meta-analysis demonstrates that 5HT2A C10T, but not 5HTTLPR (L/S), might increase risk for AD.