The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

Anthony Au; Lyn R Griffiths; Looi Irene; Cheah Wee Kooi; Loo Keat Wei

doi:10.1016/j.atherosclerosis.2017.08.003

The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

Atherosclerosis. 2017 Oct:265:60-70. doi: 10.1016/j.atherosclerosis.2017.08.003. Epub 2017 Aug 19.

Authors

Anthony Au¹, Lyn R Griffiths², Looi Irene³, Cheah Wee Kooi⁴, Loo Keat Wei⁵

Affiliations

¹ Institute of Bioproduct Development and Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, 81300 Johor, Malaysia.
² Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia.
³ Department of Medicine and Clinical Research Centre, Seberang Jaya Hospital, 13700 Seberang Jaya, Pulau Pinang, Malaysia.
⁴ Department of Medicine and Clinical Research Centre, Taiping Hospital, 34000 Taiping, Perak, Malaysia.
⁵ Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Bandar Barat, 31900 Kampar, Perak, Malaysia. Electronic address: wynnelkw@gmail.com.

PMID: 28865324
DOI: 10.1016/j.atherosclerosis.2017.08.003

Abstract

Background and aims: Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk.

Methods: A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models.

Results: A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.

Conclusions: The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke.

Keywords: ABCA1; APOA5; APOB; APOC3; Atherosclerosis; Ischemic stroke; Meta-analysis; Polymorphisms.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

ATP Binding Cassette Transporter 1 / genetics*
Apolipoprotein A-V / genetics*
Apolipoprotein B-100 / genetics*
Apolipoprotein C-III / genetics*
Brain Ischemia / diagnosis
Brain Ischemia / genetics*
Case-Control Studies
Chi-Square Distribution
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide*
Risk Factors
Stroke / diagnosis
Stroke / genetics*

Substances

ABCA1 protein, human
APOA5 protein, human
APOB protein, human
ATP Binding Cassette Transporter 1
Apolipoprotein A-V
Apolipoprotein B-100
Apolipoprotein C-III