Fang-Fang Zeng, Jun Liu, Hong He, Xu-Ping Gao, Min-Qi Liao, Xiao-Xuan Yu, Yan-Hua Liu, Sui Zhu and Chun-Xia Jing*
Background: Previous studies have examined the roles of three polymorphisms (rs3851179, rs541458, and rs592297) of the PICALM gene in susceptibility to Alzheimer's disease (AD) with inconclusive findings.
Objective: We performed a meta-analysis to explore whether these three polymorphisms in the PICALM gene were associated with susceptibility to AD.
Methods: Bibliographical searches were conducted in the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in a random effects model. Potential sources of heterogeneity were identified by subgroup and meta-regression analyses.
Results: Twenty studies (9,017 cases and 15,448 controls) on rs3851179, 12 studies (8,077 cases and 12,022 controls) on rs541458, and 4 studies (2,106 cases and 2,234 controls) on rs592297 were considered eligible for meta-analyses. For both rs3851179 and rs541458, the overall ORs were significant under all genetic models with mild heterogeneity. Compared with G carriers, A carriers of rs3851179 were associated with a decreased risk of AD (OR = 0.88; 95% CI 0.84, 0.91, P for Z-test <0.001, I 2 = 0.0%). Compared with T carriers, C carriers of rs541458 were inversely associated with AD risk (OR = 0.86; 95% CI 0.81, 0.92, P for Z-test <0.001, I 2 = 39.5%). No association was observed for rs592297. Subgroup and meta-regression analyses indicated that the protective effect of the rs541458 C allele was observed only among Caucasians, not among Asians (P for interaction: 0.021~<0.001).
Conclusion: rs3851179 and rs541458 appear to be associated with decreased AD risk. The null associations for rs592297 with AD risk need further confirmation with a larger number of participants.
Gene Polymorphisms, Alzheimer's disease
Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510630, Department of preventive medicine laboratory, School of Public Health, Zunyi Medical University, Zunyi, 563006, Health Care and Physical Examination Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510630, Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510630, Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510630, TheÂ FirstÂ AffiliatedÂ HospitalÂ ofÂ ZhengzhouÂ University, No.Â 1Â EastÂ JiansheÂ Road, Zhengzhou 450052, Henan, Department of Medical Statistics, School of Medicine, Jinan University, No.601 Huangpu Road West, Guangzhou 510632, Guangdong, Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510630