Intake levels of dietary polyunsaturated fatty acids modify the association between the genetic variation in PCSK5 and HDL cholesterol

Background: A low serum level of high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 5 (PCSK5) modulates HDL-C metabolism through the inactivation of endothelial lipase activity.

Methods: Therefore, we analysed the effects of PCSK5 on HDL-C and investigated the association between genetic variation in PCSK5 and dietary polyunsaturated fatty acids (PUFAs) intakes in Korean adults and children. This population-based study which was conducted in South Korea included 4205 adults (43% male) aged 40-69 years and 1548 children (48.6% boys) aged 8-13 years. Dietary intake was assessed using a semiquantitative food frequency questionnaire in adults and modified 3-day food records in children.

Results: After adjustments for age and body mass index, we identified a significant association between SNP rs1029035 of the PCSK5 gene and HDL-C concentrations specifically for men in both populations (adults, p=0.004; children, p=0.003; meta, p=7×10(-4)). Additionally, the interaction between the PCSK5 rs1029035 genotype and dietary polyunsaturated fatty acids intake influenced serum HDL-C concentrations in men (adults, p=0.001; children, p=0.008). The deleterious effect of the C allele on serum HDL-C was present only when dietary PUFA intake was less than the dichotomised median level (adults, p=0.011; children, p=0.001). Serum HDL-C concentrations were decreased in men with the C allele genotype and low consumption of dietary PUFA including n-3 and n-6.

Conclusion: According to these results, men carrying of the C allele were associated with low HDL-C concentrations and might exert beneficial effects on HDL-C concentrations following consumption of a high-PUFA diet.