Associations of PRKN\u2013PACRG SNPs and G\u2009\xd7\u2009G and G\u2009\xd7\u2009E interactions with the risk of hyperlipidaemia

Abstract

This research aimed to assess the associations of 7 parkin RBR E3 ubiquitin protein ligase (PRKN) and 4 parkin coregulated gene (PACRG) single-nucleotide polymorphisms (SNPs), their haplotypes, gene–gene (G × G) and gene-environment (G × E) interactions with hyperlipidaemia in the Chinese Maonan minority. The genotypes of the 11 SNPs in 912 normal and 736 hyperlipidaemic subjects were detected with next-generation sequencing technology. The genotypic and allelic frequencies of the rs1105056, rs10755582, rs2155510, rs9365344, rs11966842, rs6904305 and rs11966948 SNPs were different between the normal and hyperlipidaemic groups (P < 0.05–0.001). Correlations between the above 7 SNPs and blood lipid levels were also observed (P < 0.0045–0.001, P < 0.0045 was considered statistically significant after Bonferroni correction). Strong linkage disequilibrium was found among the 11 SNPs (r2 = 0.01–0.64). The most common haplotypes were PRKN C-G-T-G-T-T-C (> 15%) and PACRG A-T-A-T (> 40%). The PRKN C-G-C-A-T-T-C and PRKN–PACRG C-G-T-G-T-T-C-A-T-A-T haplotypes were associated with an increased risk of hyperlipidaemia, whereas the PRKN–PACRG C-G-T-G-C-T-C-A-T-C-T and C-G-T-G-T-T-C-A-T-C-T haplotypes provided a protective effect. Association analysis based on the haplotypes and G × G interaction could improve the power to detect the risk of hyperlipidaemia over the analysis of any one SNP alone. The differences in serum lipid parameters between the hyperlipidaemic and normal groups might partly be due to the effects of the PRKN–PACRG SNPs and their haplotypes.