Apolipoprotein A53'-UTR variants and cardiometabolic traits in Koreans: results from the Korean genome and epidemiology study and the Korea National Health and Nutrition Examination Survey

BACKGROUND/OBJECTIVES:This study aimed to test the association between APOA5 3'-UTR variants (rs662799) and cardiometabolic traits in Koreans.SUBJECTS/METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained.APOA5 mRNA expression was also measured.RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports.In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes.Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [β = -2.048,P < 0.001; β = -2.199,P < 0.001] as well as elevation of circulating triglyceride levels [β = 0.053, P < 0.001; β = 0.066, P < 0.001] in both the KoGES-ASAS and KNHANES groups.In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = -0.277,P = 0.027) and circulating triglyceride level (r = -0.340,P = 0.006) but not significantly correlated with circulating HDL cholesterol level.On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms.CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES.The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.