Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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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

  • Kim, Oh Yoen (Department of Food Science and Nutrition, Dong-A University) ;
  • Moon, Jiyoung (Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University) ;
  • Jo, Garam (Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University) ;
  • Kwak, So-Young (Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University) ;
  • Kim, Ji Young (Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University) ;
  • Shin, Min-Jeong (Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University)
  • Received : 2017.10.23
  • Accepted : 2017.12.18
  • Published : 2018.02.01
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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 [${\beta}=-2.048$, P < 0.001; ${\beta}=-2.199$, P < 0.001] as well as elevation of circulating triglyceride levels [${\beta}=0.053$, P < 0.001; ${\beta}=0.066$, 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.

Keywords

References

  1. Tomkin GH, Owens D. Diabetes and dyslipidemia: characterizing lipoprotein metabolism. Diabetes Metab Syndr Obes 2017;10:333-43. https://doi.org/10.2147/DMSO.S115855
  2. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Boren J, Catapano AL, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Nordestgaard BG, Ray KK, Reiner Z, Taskinen MR, Tokgozoglu L, Tybjaerg-Hansen A, Watts GF; European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and highdensity lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61. https://doi.org/10.1093/eurheartj/ehr112
  3. Lehto S, Ronnemaa T, Haffner SM, Pyorala K, Kallio V, Laakso M. Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM. Diabetes 1997;46:1354-9. https://doi.org/10.2337/diab.46.8.1354
  4. Teno S, Uto Y, Nagashima H, Endoh Y, Iwamoto Y, Omori Y, Takizawa T. Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. Diabetes Care 2000;23:1401-6. https://doi.org/10.2337/diacare.23.9.1401
  5. Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 2001;294:169-73. https://doi.org/10.1126/science.1064852
  6. Fruchart-Najib J, Bauge E, Niculescu LS, Pham T, Thomas B, Rommens C, Majd Z, Brewer B, Pennacchio LA, Fruchart JC. Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5. Biochem Biophys Res Commun 2004;319:397-404. https://doi.org/10.1016/j.bbrc.2004.05.003
  7. Schaap FG, Rensen PC, Voshol PJ, Vrins C, van der Vliet HN, Chamuleau RA, Havekes LM, Groen AK, van Dijk KW. ApoAV reduces plasma triglycerides by inhibiting very low density lipoproteintriglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis. J Biol Chem 2004;279:27941-7. https://doi.org/10.1074/jbc.M403240200
  8. van der Vliet HN, Sammels MG, Leegwater AC, Levels JH, Reitsma PH, Boers W, Chamuleau RA. Apolipoprotein A-V: a novel apolipoprotein associated with an early phase of liver regeneration. J Biol Chem 2001;276:44512-20. https://doi.org/10.1074/jbc.M106888200
  9. Lim HH, Choi M, Kim JY, Lee JH, Kim OY. Increased risk of obesity related to total energy intake with the APOA5-1131T > C polymorphism in Korean premenopausal women. Nutr Res 2014;34:827-36. https://doi.org/10.1016/j.nutres.2014.08.018
  10. Lee KH, Kim OY, Lim HH, Lee YJ, Jang Y, Lee JH. Contribution of APOA5-1131C allele to the increased susceptibility of diabetes mellitus in association with higher triglyceride in Korean women. Metabolism 2010;59:1583-90. https://doi.org/10.1016/j.metabol.2010.02.008
  11. Wang Y, Lu Z, Zhang J, Yang Y, Shen J, Zhang X, Song Y. The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women. Lipids Health Dis 2016;15:170-8. https://doi.org/10.1186/s12944-016-0343-z
  12. Pennacchio LA, Olivier M, Hubacek JA, Krauss RM, Rubin EM, Cohen JC. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 2002;11:3031-8. https://doi.org/10.1093/hmg/11.24.3031
  13. Hubacek JA, Skodova Z, Adamkova V, Lanska V, Poledne R. The influence of APOAV polymorphisms (T-1131 > C and S19 >W) on plasma triglyceride levels and risk of myocardial infarction. Clin Genet 2004;65:126-30. https://doi.org/10.1111/j.0009-9163.2004.00199.x
  14. Hubacek JA, Kovar J, Skodova Z, Pit'ha J, Lanska V, Poledne R. Genetic analysis of APOAV polymorphisms (T-1131/C, Ser19/Trp and Val153/Met): no effect on plasma remnant particles concentrations. Clin Chim Acta 2004;348:171-5. https://doi.org/10.1016/j.cccn.2004.05.011
  15. Lee KW, Ayyobi AF, Frohlich JJ, Hill JS. APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease. Atherosclerosis 2004;176:165-72. https://doi.org/10.1016/j.atherosclerosis.2004.04.024
  16. Kim Y, Han BG; KoGES group. Cohort profile: the Korean Genome and Epidemiology Study (KoGES) Consortium. Int J Epidemiol 2017;46:e20. https://doi.org/10.1093/ije/dyv316
  17. Kweon S, Kim Y, Jang MJ, Kim Y, Kim K, Choi S, Chun C, Khang YH, Oh K. Data resource profile: the Korea National Health and Nutrition Examination Survey (KNHANES). Int J Epidemiol 2014;43:69-77. https://doi.org/10.1093/ije/dyt228
  18. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, O'Brien WL, Bassett DR Jr, Schmitz KH, Emplaincourt PO, Jacobs DR Jr, Leon AS. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32:S498-504. https://doi.org/10.1097/00005768-200009001-00009
  19. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ, Park M, Cha SH, Kim JW, Han BG, Min H, Ahn Y, Park MS, Han HR, Jang HY, Cho EY, Lee JE, Cho NH, Shin C, Park T, Park JW, Lee JK, Cardon L, Clarke G, McCarthy MI, Lee JY, Lee JK, Oh B, Kim HL. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009;41:527-34. https://doi.org/10.1038/ng.357
  20. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  21. Pi Y, Zhang L, Yang Q, Li B, Guo L, Fang C, Gao C, Wang J, Xiang J, Li J. Apolipoprotein A5 gene promoter region-1131T/C polymorphism is associated with risk of ischemic stroke and elevated triglyceride levels: a meta-analysis. Cerebrovasc Dis 2012;33:558-65. https://doi.org/10.1159/000338781
  22. Zhang Z, Peng B, Gong RR, Gao LB, Du J, Fang DZ, Song YY, Li YH, Ou GJ. Apolipoprotein A5 polymorphisms and risk of coronary artery disease: a meta-analysis. Biosci Trends 2011;5:165-72. https://doi.org/10.5582/bst.2011.v5.4.165
  23. Au A, Griffiths LR, Irene L, Kooi CW, Wei LK. The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: evidence from a meta-analysis. Atherosclerosis 2017;265:60-70. https://doi.org/10.1016/j.atherosclerosis.2017.08.003
  24. Talmud PJ, Palmen J, Putt W, Lins L, Humphries SE. Determination of the functionality of common APOA5 polymorphisms. J Biol Chem 2005;280:28215-20. https://doi.org/10.1074/jbc.M502144200
  25. Yan SK, Cheng XQ, Song YH, Xiao XH, Bi N, Chen BS. 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 2005;43:607-12.
  26. Endo K, Yanagi H, Araki J, Hirano C, Yamakawa-Kobayashi K, Tomura S. Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren. Hum Genet 2002;111:570-2. https://doi.org/10.1007/s00439-002-0825-0
  27. Perez-Martinez P, Corella D, Shen J, Arnett DK, Yiannakouris N, Tai ES, Orho-Melander M, Tucker KL, Tsai M, Straka RJ, Province M, Kai CS, Perez-Jimenez F, Lai CQ, Lopez-Miranda J, Guillen M, Parnell LD, Borecki I, Kathiresan S, Ordovas JM. 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 2009;89:391-9. https://doi.org/10.3945/ajcn.2008.26363
  28. Prieur X, Coste H, Rodriguez JC. 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 2003;278:25468-80. https://doi.org/10.1074/jbc.M301302200
  29. Vaessen SF, Schaap FG, Kuivenhoven JA, Groen AK, Hutten BA, Boekholdt SM, Hattori H, Sandhu MS, Bingham SA, Luben R, Palmen JA, Wareham NJ, Humphries SE, Kastelein JJ, Talmud PJ, Khaw KT. Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study. J Lipid Res 2006;47:2064-70. https://doi.org/10.1194/jlr.M600233-JLR200
  30. Caussy C, Charriere S, Marcais C, Di Filippo M, Sassolas A, Delay M, Euthine V, Jalabert A, Lefai E, Rome S, Moulin P. 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 2014;94:129-34. https://doi.org/10.1016/j.ajhg.2013.12.001
  31. Lim MY, You HJ, Yoon HS, Kwon B, Lee JY, Lee S, Song YM, Lee K, Sung J, Ko G. The effect of heritability and host genetics on the gut microbiota and metabolic syndrome. Gut 2017;66:1031-8. https://doi.org/10.1136/gutjnl-2015-311326
  32. Ahn HY, Kim M, Chae JS, Ahn YT, Sim JH, Choi ID, Lee SH, Lee JH. 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 2015;241:649-56. https://doi.org/10.1016/j.atherosclerosis.2015.06.030
  33. Guardiola M, Alvaro A, Vallve JC, Rosales R, Sola R, Girona J, Serra N, Duran P, Esteve E, Masana L, Ribalta J. APOA5 gene expression in the human intestinal tissue and its response to in vitro exposure to fatty acid and fibrate. Nutr Metab Cardiovasc Dis 2012;22:756-62. https://doi.org/10.1016/j.numecd.2010.12.003
  34. Zhang LS, Xu M, Yang Q, Ryan RO, Howles P, Tso P. Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice. Am J Physiol Gastrointest Liver Physiol 2015;308:G634-42. https://doi.org/10.1152/ajpgi.00339.2014
  35. Oliva I, Guardiola M, Vallve JC, Ibarretxe D, Plana N, Masana L, Monk D, Ribalta J. APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels. Clin Sci (Lond) 2016;130:2053-9. https://doi.org/10.1042/CS20160433

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