Genetics of Vascular Dementia: Systematic Review and Meta-Analysis

Article type: Research Article

Authors: Sun, Jia-Hao^a | Tan, Lan^{a; b; c; *} | Wang, Hui-Fu^b | Tan, Meng-Shan^a | Tan, Lin^c | Li, Jie-Qiong^a | Xu, Wei^a | Zhu, Xi-Chen^b | Jiang, Teng^d | Yu, Jin-Tai^{a; b; e; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China | [b] Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China | [c] College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China | [d] Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China | [e] Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA

Correspondence: [*] Correspondence to: Dr. Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province 266071, China. E-mail: [email protected]

Correspondence: [*] Correspondence to: Jin-Tai Yu, Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA 94158, USA. Tel./Fax: 001 415 514 5745; E-mail: [email protected] or [email protected]

Abstract: Background: Vascular dementia (VaD) is the second most common type of dementia. So far, little is known about the contribution of genetic polymorphisms to the risk of VaD. Many candidate genetic polymorphisms have been examined in a large number of studies. However, due to the conflicting results, the genetics of VaD is still behind the shadow. Objective: We conducted a comprehensive meta-analysis on associations between genetic polymorphisms of any gene and VaD to investigate the genetics of VaD. Method: We sought the published studies of associations between any genetic polymorphism and VaD and critically appraised them. We assessed the effects of genetic models by calculating pooled odds ratios (ORs), investigating the origin of heterogeneity by subgroup analysis, and testing the robustness by random effect model and sensitivity analysis. Results: 69 studies with 4,462 cases and 11,583 controls were included. We identified APOE ɛ2/ɛ3/ɛ4 and additional four genetic polymorphisms including MTHFR C677T, PON1 L55M, TGF-β1 +29C/T, and TNF-α −850C/T associated with VaD. Tested by random effect model and sensitivity analysis, the pooled results show nice robustness. Conclusions: Our comprehensive meta-analysis highlighted the genetic contribution to sporadic VaD. Because of the small amount of data on associations between genetic polymorphisms, except for APOE, and VaD, more studies are needed to test the existing genetic polymorphisms and detect other related genetic variants.

Keywords: Apolipoprotein E, dementia, genetics, polymorphism, vascular dementia

DOI: 10.3233/JAD-143102

Journal: Journal of Alzheimer's Disease, vol. 46, no. 3, pp. 611-629, 2015