Unravelling the Influence of Apolipoprotein A5 Gene Polymorphisms on Lipid Profiles of Statin-Treated Patients: A Scoping Review
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Abstract
The apolipoprotein A5 (APOA5) protein plays a critical role in lipid metabolism, particularly in the regulation of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Given the scattered nature of existing data, this review aims to consolidate current knowledge on APOA5 gene polymorphisms and their effects on lipid profiles among statin users. Using Arksey and O’Malley’s framework, a systematic search was performed encompassing studies published between April 2002 and April 2026. From 617 titles initially identified, 14 studies met the inclusion criteria and were reviewed narratively by two independent reviewers. Two single nucleotide polymorphisms (SNPs) in the APOA5 gene, rs662799 (c.-1131T>C) and rs3135506 (c.56C>G), were consistently associated with TG and HDL‑C levels in individuals receiving statin monotherapy or combination lipid-lowering treatment. Carriers of the minor alleles exhibited higher baseline and on-treatment TG levels, accompanied by lower HDL‑C, indicating a greater predisposition to hypertriglyceridaemia (HTG). The influence of these variants was more pronounced before statin initiation, while post-treatment associations were variable. Evidence for the impact of APOA5 polymorphisms on low-density lipoprotein cholesterol (LDL-C) was limited, suggesting that statin-induced LDL-C reduction may override genetic effects. Additionally, APOA5 variants have been linked to differential lipid responses to selected plant-derived lipid-lowering agents. Polymorphisms in the APOA5 gene appear to modulate TG and HDL‑C levels significantly, but not LDL-C, highlighting their potential utility as biomarkers for hyperlipidaemia and personalised lipid-lowering strategies in statin-treated individuals. Further functional and metabolomic studies are needed to clarify their mechanistic roles.
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