Associations of ANGPTL6, DOCK6, FABP1, and PCSK9 single nucleotide variants and hypercholesterolemia in the Polish population: a cross-sectional study

Hypercholesterolemia is a chronic non-communicable disease predisposing to cardiovascular diseases. Genome-wide association studies have shown that more than 500 common nucleotide variants are associated with dyslipidemia.We evaluated associations between selected nucleotide variants in ANGPTL6, DOCK6, FABP1, and PCSK9 genes and hypercholesterolemia in the Polish adult population sample.The study included 109 patients with hypercholesterolemia and 251 individuals with no diagnosed lipid disorder. Genotyping of ANGPTL6 rs8112063, DOCK6 rs737337 and rs17699089, FABP1 rs2241883 and rs2919872, and PCSK9 rs562556 and rs11206510 was carried out using high resolution melting curve analysis. The serum concentrations of FABP1, PCSK9, ANGPTL6, and ANGPTL8 were determined in 51 subjects by enzyme-linked immunosorbent assay. Results: Bearers of the FABP1 rs2919872 CC genotype were over 2.5-fold less likely to be diagnosed with hypercholesterolemia than the carriers of the T allele (OR 0.386 95% CI 0.203 - 0.735, p = 0.003, pcorr = 0.006). There were no associations between rs2919872 and lipid serum concentrations. Bearers of the ANGPTL6 rs8112063 C allele had an almost 2-fold higher risk of developing hypercholesterolemia than the carriers of the T allele (OR 1.820 95%CI 1.053 - 3.144, p = 0.03, pcorr = 0.046). Moreover, the bearers of the ANGPTL6 rs8112063 C allele had higher serum concentrations of HDL-cholesterol than those with TT genotype (p = 0.009). There were no significant associations between the other tested variants and hypercholesterolemia.FABP1 rs2919872 and ANGPTL6 rs8112063 are associated with the risk of hypercholesterolemia in the Polish population.