Apolipoprotein A5 3'-UTR variants and cardiometabolic traits in Koreans: results from the Korean genome and epidemiology study and the Korea National Health and Nutrition Examination Survey
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
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.
Abstract
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.
참고문헌 (35)
- Tomkin GH, "Diabetes and dyslipidemia: characterizing lipoprotein metabolism", Diabetes Metab Syndr Obes, 10, pp.333~343 (2017)[DOI]
- Chapman MJ, "Triglyceride-rich lipoproteins and highdensity lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management", Eur Heart J, 32, pp.1345~1361 (2011)[DOI]
- Lehto S, "Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM", Diabetes, 46, pp.1354~1359 (1997)[DOI]
- Teno S, "Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes", Diabetes Care, 23, pp.1401~1406 (2000)[DOI]
- Pennacchio LA, "An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing", Science, 294, pp.169~173 (2001)[DOI]
- Fruchart-Najib J, "Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5", Biochem Biophys Res Commun, 319, pp.397~404 (2004)[DOI]
- Schaap FG, "ApoAV reduces plasma triglycerides by inhibiting very low density lipoproteintriglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis", J Biol Chem, 279, pp.27941~27947 (2004)[DOI]
- van der Vliet HN, "Apolipoprotein A-V: a novel apolipoprotein associated with an early phase of liver regeneration", J Biol Chem, 276, pp.44512~44520 (2001)[DOI]
- Lim HH, "Increased risk of obesity related to total energy intake with the APOA5-1131T > C polymorphism in Korean premenopausal women", Nutr Res, 34, pp.827~836 (2014)[DOI]
- Lee KH, "Contribution of APOA5-1131C allele to the increased susceptibility of diabetes mellitus in association with higher triglyceride in Korean women", Metabolism, 59, pp.1583~1590 (2010)[DOI]
- Wang Y, "The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women", Lipids Health Dis, 15, pp.170~178 (2016)[DOI]
- Pennacchio LA, "Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels", Hum Mol Genet, 11, pp.3031~3038 (2002)[DOI]
- Hubacek JA, "The influence of APOAV polymorphisms (T-1131 > C and S19 >W) on plasma triglyceride levels and risk of myocardial infarction", Clin Genet, 65, pp.126~130 (2004)[DOI]
- Hubacek JA, "Genetic analysis of APOAV polymorphisms (T-1131", C, Ser19, Met): no effect on plasma remnant particles concentrations, pp.Clin Chim Acta, 2004[DOI]
- Lee KW, "APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease", Atherosclerosis, 176, pp.165~172 (2004)[DOI]
- Kim Y, "Cohort profile: the Korean Genome and Epidemiology Study (KoGES) Consortium", Int J Epidemiol, 46, pp.e20~ (2017)[DOI]
- Kweon S, "Data resource profile: the Korea National Health and Nutrition Examination Survey (KNHANES)", Int J Epidemiol, 43, pp.69~77 (2014)[DOI]
- Ainsworth BE, "Compendium of physical activities: an update of activity codes and MET intensities", Med Sci Sports Exerc, 32, pp.S498~S504 (2000)[DOI]
- Cho YS, "A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits", Nat Genet, 41, pp.527~534 (2009)[DOI]
- Friedewald WT, "Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge", Clin Chem, 18, pp.499~502 (1972)
- Pi Y, "Apolipoprotein A5 gene promoter region-1131T", C polymorphism is associated with risk of ischemic stroke and elevated triglyceride levels: a meta-analysis, 2012, pp.33, 558~565
- Zhang Z, "Apolipoprotein A5 polymorphisms and risk of coronary artery disease: a meta-analysis", Biosci Trends, 5, pp.165~172 (2011)[DOI]
- Au A, "The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: evidence from a meta-analysis", Atherosclerosis, 265, pp.60~70 (2017)[DOI]
- Talmud PJ, "Determination of the functionality of common APOA5 polymorphisms", J Biol Chem, 280, pp.28215~28220 (2005)[DOI]
- Yan SK, "Apolipoprotein A5 gene polymorphism -1131T-->C: association with plasma lipids and type 2 diabetes mellitus with coronary heart disease in Chinese", Clin Chem Lab Med, 43, pp.607~612 (2005)
- Endo K, "Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren", Hum Genet, 111, pp.570~572 (2002)[DOI]
- Perez-Martinez P, "Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states", Am J Clin Nutr, 89, pp.391~399 (2009)[DOI]
- Prieur X, "The human apolipoprotein AV gene is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element", J Biol Chem, 278, pp.25468~25480 (2003)[DOI]
- Vaessen SF, "Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study", J Lipid Res, 47, pp.2064~2070 (2006)[DOI]
- Caussy C, "An APOA5 3' UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site", Am J Hum Genet, 94, pp.129~134 (2014)[DOI]
- Lim MY, "The effect of heritability and host genetics on the gut microbiota and metabolic syndrome", Gut, 66, pp.1031~1038 (2017)[DOI]
- Ahn HY, "Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia", Atherosclerosis, 241, pp.649~656 (2015)[DOI]
- Guardiola M, "APOA5 gene expression in the human intestinal tissue and its response to in vitro exposure to fatty acid and fibrate", Nutr Metab Cardiovasc Dis, 22, pp.756~762 (2012)[DOI]
- Zhang LS, "Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice", Am J Physiol Gastrointest Liver Physiol, 308, pp.G634~G642 (2015)[DOI]
- Oliva I, "APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels", Clin Sci (Lond), 130, pp.2053~2059 (2016)[DOI]