PLTP Variants rs6065904 and rs378114 Are Associated with Acute Coronary Syndrome Risk and Altered Glucose and Triglyceride Levels in a Mexican Population

Background: Phospholipid transfer protein (PLTP) facilitates lipid transfer among plasma lipoproteins, but the contribution of this protein to coronary heart disease (CHD) remains controversial. In this context, evaluating single nucleotide polymorphisms (SNPs) in the PLTP gene, specifically rs6065904 A/G and rs378114 T/C, may hold clinical utility for predicting CHD risk. Nevertheless, currently evidence on the association between these variants and cardiovascular outcomes remains scarce. To address this gap, we investigated whether the rs6065904 A/G and rs378114 T/C SNPs of the PLTP gene are associated with the incidence of acute coronary syndrome (ACS) and explored whether this potential relationship is mediated by plasma lipid levels. Methods: This study included 2377 Mexican Mestizos (1378 ACS patients and 999 control individuals). The PLTP SNPs (rs6065904 A/G, and rs378114 T/C) were genotyped using TaqMan assays on Real-Time PCR equipment, following the manufacturer’s cycling protocol. Results: Logistic regression analysis under different inheritance models revealed that homozygosity for the rs6065904 AA and rs378114 TT genotypes was associated with a significant increased risk of ACS. In subgroup analysis restricted to ACS patients, both genotypes were also significantly associated with altered triglyceride and glucose levels. Complementary bioinformatic analysis using the Genotype-Tissue Expression (GTEx) Project suggested that these genotype–phenotype associations might be mechanistically linked to reduced PLTP mRNA expression. Conclusions: In summary, the rs6065904 A/G and rs378114 T/C SNPs in the PLTP gene are associated with ACS risk, and with circulating triglyceride and glucose levels.