Association Between Patatin-Like Phospholipase Do-Main-Containing Protein-3 Variant and Cardiovascular Disease Risk in People Living With HIV on Antiretroviral Therapy in Taiwan

Background and Aims: Cardiovascular disease (CVD) risk is elevated among people living with HIV (PLWH), particularly those receiving antiretroviral therapy (ART). This study aimed to examine associations between single-nucleotide polymorphisms (SNPs) in lipoprotein-related genes and CVD risk among PLWH undergoing ART. Methods: Blood samples from 337 PLWH at Chung Shan Medical University Hospital were analyzed, including 238 individuals who switched ART and 99 who continued their regimen. Genotyping of four SNPs—namely, ATP binding cassette B1 (ABCB1; rs1045642), apolipoprotein E (APOE; rs429358 and rs7412), and patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409) was performed using real-time polymerase chain reaction and sequence-based typing. CVD risk scores were calculated using the D:A:D model, with high risk defined as a 10-year risk > 5%. Associations between SNPs and CVD risk scores were assessed using analysis of covariance, adjusting for demographic and clinical covariates. Results: The cohort was predominantly male 95.6% (322/337), with a mean age of 34.6 years. Metabolic abnormalities were common, and 16.0% (54/337) of participants on ART were classified as high-risk for CVD. Among the SNPs analyzed, PNPLA3 (rs738409) was significantly associated with higher D:A:D (R) 10-year CVD risk scores (p = 0.03) and showed marginal associations with 5-year risk scores (p = 0.05). The APOE (rs7412) T allele demonstrated borderline associations with increased CVD risk (p = 0.07–0.09). No significant associations were observed for ABCB1 or APOE (rs429358). PNPLA3 may influence triglyceride hydrolysis via adipose triglyceride lipase, contributing to fatty liver disease and elevating CVD risk. Conclusion: SNPs in PNPLA3 and APOE may contribute to increased CVD risk among PLWH receiving ART. Incorporating genetic screening into clinical care could support personalized treatment strategies and improve long-term CVD outcomes.