Association of OLR1 Gene Polymorphisms with the Risk of Coronary Artery Disease: A Systematic Review and Meta-analysis

Background: Oxidized LDL receptor 1 (OLR1) encodes LOX-1, LOXIN, and OLR1D4 transcript variants. Up-regulation of LOX-1 and down-regulation of LOXIN have an essential role in causing coronary artery disease (CAD). Discovery of risk single nucleotide polymorphisms (SNPs) in OLR1 gene is clinically important as these polymorphisms could be candidate biomarkers of CAD.

Objectives: The purpose of this study is quantitative evidence synthesis on how OLR1 polymorphisms in the haplotype block impact the risk of CAD.

Methods: First, a systematic keyword-based search in PubMed, Web of Science, and Scopus was conducted. After data extraction, pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for OLR1 polymorphisms and CAD. Twelve case-control studies, including 6,238 cases and 15,773 controls, were concluded in the meta-analysis.

Results: Our findings demonstrate significant association of OLR1 polymorphisms in the haplotype block with CAD risk in all genetic models (allelic model: OR = 1.19, 95%CI = 1.06-1.34; additive model: OR = 1.54, 95%CI = 1.16-2.05; recessive model: OR = 1.26, 95%CI = 1.04-1.53; dominant model: OR = 1.28, 95%CI = 1.09-1.51). Subgroup analysis based on the type of polymorphism revealed that rs1050283 (3'UTR*188 C > T) and rs3736235 (IVS4-14 A > G) are more significantly associated with the risk of CAD compared to other polymorphisms in the haplotype block.

Conclusions: We found a significant association between OLR1 polymorphisms in the haplotype block, especially rs1050283 and rs3736235, with CAD. We also suggest that precise determination of disease association with polymorphisms in a haplotype requires investigation of all SNPs rather than a single SNP in that specific haplotype.