Genetic Susceptibility Variants of Vascular Dementia among Asians: A Systematic Review and Meta-Analysis

Abstract

<b><i>Introduction:</i></b> Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous studies have investigated candidate genetic polymorphisms associated with VaD in Asia, the genetics of VaD remains unclear. <b><i>Methods:</i></b> This review provides an updated meta-analysis of genetic polymorphisms associated with VaD in Asians, using the PRISMA guidelines. Published literature up to May 2021 was extracted from the PubMed, Scopus, Ovid, and EBSCOhost databases. Meta-analysis was conducted using the Open Meta analyst, Review Manager, and MedCalc^® Statistical Software. Trial sequential analysis (TSA) was performed using TSA viewer software. <b><i>Results:</i></b> A total of 46 eligible studies, comprising 23 genes and 35 single nucleotide polymorphisms, were retrieved. The meta-analysis was conducted on the following genetic polymorphisms, <i>APOE ε2/3/4</i>, <i>MTHFR</i> rs1801131, <i>ACE</i> rs4340 (I/D) gene polymorphism, and a <i>PSEN1</i> intron 8 variant. The pooled odds ratio (ORs) revealed a significant increase in the risk of VaD in the apolipoprotein E (<i>APOE</i>) ε4 allelic model (OR, 1.79, <i>p</i> &lt; 0.001), and the methylenetetrahydrofolate reductase (<i>MTHFR</i>) rs1801133 polymorphism T allele in the allelic model (OR, 1.23, <i>p</i> = 0.013). <b><i>Conclusion:</i></b> Our findings provide evidence that genetic polymorphisms of the <i>APOE ε4 allele</i> and <i>MTHFR</i> rs1801133 T allele increase the risk of developing VaD in Asians. However, future large-scale investigations examining particularly on South-Eastern and West-Asian populations are highly recommended.