PSRC1 rs599839 G allele may promote protection from coronary artery disease in a Madeira Island population

Abstract

Abstract Previous research associates the PSRC1 gene on the chromosomal locus 1p13.3 with coronary artery disease (CAD). Specifically, the A wild allele of the PSRC1 rs599539 A>G was identified as a risk allele for CAD, and the mutated G minor allele with a reduced risk of CAD. However, the underlying genetic mechanism is not yet fully understood and is controversial in other populations. Aim To investigate the association of rs599839 A>G variant with CAD risk and lipid profile in a Portuguese population from Madeira Island. Materials and Methods We performed a case-control study including 3161 participants, 1724 patients with CAD (78.7% male) and 1437 controls (76.3% male). Coronary patients were recruited from the Madeira Central Hospital, and controls were from the normal population. PSRC1 was genotyped by TaqMan allelic discrimination assay (Applied Biosystems, 7300 Real-Time PCR). Pearson´s Chi-squared test evaluated the association between CAD-genotypes and the t Student test for genotypes-lipid levels. Results PSRC1 rs599839 A>G variant was within Hardy -Weinberg equilibrium. The wild dominant model (AA+AG) conferred a trend for CAD risk (OR=1.16; p=0.414), and the mutated dominant model (GG+GA) presented slight protection for CAD susceptibility. However, the minor G (protector) allele was associated with low levels of total cholesterol (p=0.003) and LDL-cholesterol (p=0.004). Conclusions This finding is consistent with previous reports indicating a decrease in LDL-C and total cholesterol levels in carriers of the minor allele G of rs599839. Recent research refers that this allele could affect PSRC1 expression, resulting in lower levels of LDL cholesterol and reduced risk of CAD. In contrast, the A wild allele is associated with high LDL levels. PSRC1, lipid, and CAD risk is a complex topic involving genetic, epigenetic and environmental factors.