Association of APOE genotype with lipid profiles and type 2 diabetes mellitus in a Korean population.

Publisher: The Korean Society of Genetics Country of Publication: Korea (South) NLM ID: 101481027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2092-9293 (Electronic) Linking ISSN: 19769571 NLM ISO Abbreviation: Genes Genomics Subsets: MEDLINE

Original Publication: Seoul : The Korean Society of Genetics, 2008-

Apolipoproteins E/*genetics ; Diabetes Mellitus, Type 2/*genetics ; Lipids/*blood; Alleles ; Diabetes Mellitus, Type 2/blood ; Female ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea

Background: Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia and lipid metabolism. A previous genome-wide association study revealed the TOMM40-APOE region as novel locus for T2DM susceptibility.
Objective: This association study was conducted to determine the genetic effects of APOE single nucleotide polymorphisms (SNPs) on T2DM susceptibility and lipid profiles in a Korean population.
Methods: A total of 6 tagging SNPs, including rs7412 and rs429358, were selected for ε genotype analysis and genotyped in 1436 subjects, consisting of 352 T2DM patients and 1084 unaffected controls.
Results: Logistic regression analyses were conducted and there were no significant associations among the APOE 6 tagging SNPs, ε genotypes, and haplotypes with T2DM susceptibility. To investigate the association of the APOE tagging SNPs with the lipid profiles, a regression analysis was conducted. As a result, rs7412 was significantly associated with the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels (P corr  = 2.30 × 10 ^-5 and 3.39 × 10 ^-13 , respectively) in the unaffected controls. The ε2 allele and ε3 allele were significantly associated with the TC (P corr  = 4.46 × 10 ^-6 and 0.02, respectively) and LDL levels (P corr  = 3.54 × 10 ^-14 and 0.0006, respectively) in the unaffected controls. Further analysis of only the unaffected controls was conducted. As a result, the APOE alleles ε2 and ε3 showed a significant association with the TC and LDL levels (P < 0.05).
Conclusion: The results of this study may help in understanding APOE polymorphisms and ε alleles and lipid profiles, which have been highly linked to T2DM, in a Korean population.

Afroze D, Yousuf A, Tramboo NA, Shah ZA, Ahmad A (2016) ApoE gene polymorphism and its relationship with coronary artery disease in ethnic Kashmiri population. Clin Exp Med 16:551–556. (PMID: 26409839)
Alharbi KK, Khan IA, Syed R (2014) Association of apolipoprotein E polymorphism with type 2 diabetes mellitus in a Saudi population. DNA Cell Biol 33:637–641. (PMID: 24979464)
Ali O (2013) Genetics of type 2 diabetes. World J Diabetes 4:114–123. (PMID: 239613213746083)
Alvim RO, Freitas SR, Ferreira NE, Santos PC, Cunha RS, Mill JG, Krieger JE, Pereira AC (2010) APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population. Lipids Health Dis 9:128. (PMID: 210591962992057)
Baars HF, SmagtDoevendans JJVDPA (2011) Clinical cardiogenetics. Springer, London.
Barbosa EJ, Glad CA, Nilsson AG, Filipsson Nystrom H, Gotherstrom G, Svensson PA, Vinotti I, Bengtsson BA, Nilsson S, Boguszewski CL et al (2012) Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy. Eur J Endocrinol 167:353–362. (PMID: 22715478)
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265. (PMID: 15297300)
Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U et al (2007) Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 298:1300–1311. (PMID: 17878422)
Bennet AM, Reynolds CA, Gatz M, Blennow K, Pedersen NL, Prince JA (2010) Pleiotropy in the presence of allelic heterogeneity: alternative genetic models for the influence of APOE on serum LDL, CSF amyloid-beta42, and dementia. J Alzheimers Dis 22:129–134. (PMID: 208474323547982)
Boerwinkle E, Utermann G (1988) Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism. Am J Hum Genet 42:104–112. (PMID: 33371041715322)
Chaudhary R, Likidlilid A, Peerapatdit T, Tresukosol D, Srisuma S, Ratanamaneechat S, Sriratanasathavorn C (2012) Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovasc Diabetol 11:36. (PMID: 225209403372424)
Cook JP, Morris AP (2016) Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility. Eur J Hum Genet 24:1175–1180. (PMID: 271890214947384)
Daniel MJ (2011) Lipid management in patients with type 2 diabetes. Am Health Drug Benefits 4:312–322. (PMID: 251263594105726)
American Diabetes Association (2009) Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 32(Suppl 1):S62–S67. (PMID: 2613584)
Dong LM, Parkin S, Trakhanov SD, Rupp B, Simmons T, Arnold KS, Newhouse YM, Innerarity TL, Weisgraber KH (1996) Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia. Nat Struct Biol 3:718–722. (PMID: 8756331)
Dong LM, Weisgraber KH (1996) Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins. J Biol Chem 271:19053–19057. (PMID: 8702576)
Dong LM, Wilson C, Wardell MR, Simmons T, Mahley RW, Weisgraber KH, Agard DA (1994) Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. J Biol Chem 269:22358–22365. (PMID: 8071364)
Duman BS, Ozturk M, Yilmazer S, Hatemi H (2004) Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus: allele frequency and relation to serum lipid concentrations. Diabetes Nutr Metab 17:267–274. (PMID: 16295048)
El-Lebedy D, Raslan HM, Mohammed AM (2016) Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease. Cardiovasc Diabetol 15:12. (PMID: 268008924724147)
Florez JC, Hirschhorn J, Altshuler D (2003) The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu Rev Genom Hum Genet 4:257–291.
Frieden C (2015) ApoE: the role of conserved residues in defining function. Protein Sci 24:138–144. (PMID: 25377861)
Getz GS, Reardon CA (2009) Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall. J Lipid Res 50(Suppl):S156-161. (PMID: 190180382674757)
Guang-da X, You-ying L, Zhi-song C, Yu-sheng H, Xiang-jiu Y (2004) Apolipoprotein e4 allele is predictor of coronary artery disease death in elderly patients with type 2 diabetes mellitus. Atherosclerosis 175:77–81. (PMID: 15186949)
Haffner SM (2004) Dyslipidemia management in adults with diabetes. Diabetes Care 27(Suppl 1):S68-71. (PMID: 14693930)
Horejsi B, Ceska R (2000) Apolipoproteins and atherosclerosis. Apolipoprotein E and apolipoprotein(a) as candidate genes of premature development of atherosclerosis. Physiol Res 49(Suppl 1):S63-69. (PMID: 10984073)
Hu FB (2003) Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids 38:103–108. (PMID: 12733740)
Inzucchi SE, Amatruda JM (2003) Lipid management in patients with diabetes: translating guidelines into action. Diabetes Care 26:1309–1311. (PMID: 12663615)
Jeenduang N, Porntadavity S, Wanmasae S (2015) Combined PCSK9 and APOE polymorphisms are genetic risk factors associated with elevated plasma lipid levels in a Thai population. Lipids 50:543–553. (PMID: 25899039)
Kalina A, Szalai C, Prohaszka Z, Reiber I, Csaszar A (2002) Association of plasma lipid levels with apolipoprotein E polymorphism in Type 2 diabetes. Diabetes Res Clin Pract 56:63–68. (PMID: 11879722)
Kim YS, Paeng JR, Woo JT, Kim SW, Yang IM, Kim JW, Kim KW, Choi YK (1993) Apolipoprotein E genotypes of normal and hyperlipidemic subjects. J Korean Med Sci 8:262–266. (PMID: 81987633053758)
Larifla L, Armand C, Bangou J, Blanchet-Deverly A, Numeric P, Fonteau C, Michel CT, Ferdinand S, Bourrhis V, Velayoudom-Cephise FL (2017) Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans. PLoS ONE 12:e0181620. (PMID: 287278555519172)
Lee YJ, Jang HC, Kim EH, Kim HJ, Lee SB, Choi SH, Lim S, Park KU, Park YJ, Kim KW (2008) Association between apolipoprotein E polymorphism and type 2 diabetes in subjects aged 65 or over. Korean Diabetes J 32:30.
Leiva E, Mujica V, Orrego R, Prieto M, Arredondo M (2005) Apolipoprotein E polymorphism in type 2 diabetic patients of Talca, Chile. Diabetes Res Clin Pract 68:244–249. (PMID: 15936467)
Liu M, Bian C, Zhang J, Wen F (2014) Apolipoprotein E gene polymorphism and Alzheimer’s disease in Chinese population: a meta-analysis. Sci Rep 4:4383. (PMID: 246328493955907)
Ozder A (2014) Lipid profile abnormalities seen in T2DM patients in primary healthcare in Turkey: a cross-sectional study. Lipids Health Dis 13:183. (PMID: 254811154271485)
Phillips MC (2014) Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life 66:616–623. (PMID: 25328986)
Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance—a population-based twin study. Diabetologia 42:139–145. (PMID: 10064092)
Radwan ZH, Wang X, Waqar F, Pirim D, Niemsiri V, Hokanson JE, Hamman RF, Bunker CH, Barmada MM, Demirci FY et al (2014) Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. whites and African blacks. PLoS ONE 9:e114618. (PMID: 255028804264772)
Raj R, Bhatti JS, Badada SK, Ramteke PW (2015) Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM). Diabetes Metab Res Rev 31:663–671. (PMID: 25470794)
Rall SC Jr, Mahley RW (1992) The role of apolipoprotein E genetic variants in lipoprotein disorders. J Intern Med 231:653–659. (PMID: 1619388)
Rall SC Jr, Weisgraber KH, Mahley RW (1982) Human apolipoprotein E. The complete amino acid sequence. J Biol Chem 257:4171–4178. (PMID: 7068630)
Rasmussen KL (2016) Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: a review. Atherosclerosis 255:145–155. (PMID: 28340945)
Saydah SH, Fradkin J, Cowie CC (2004) Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 291:335–342. (PMID: 14734596)
Shin MH, Kim HN, Cui LH, Kweon SS, Park KS, Heo H, Nam HS, Jeong SK, Chung EK, Choi JS (2005) The effect of apolipoprotein E polymorphism on lipid levels in Korean adults. J Korean Med Sci 20:361–366. (PMID: 159538532782187)
Sing CF, Davignon J (1985) Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 37:268–285. (PMID: 39850081684560)
Singh PP, Naz I, Gilmour A, Singh M, Mastana S (2006) Association of APOE (Hha1) and ACE (I/D) gene polymorphisms with type 2 diabetes mellitus in North West India. Diabetes Res Clin Pract 74:95–102. (PMID: 16621107)
Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989. (PMID: 112544541275651)
Vijayaraghavan K (2010) Treatment of dyslipidemia in patients with type 2 diabetes. Lipids Health Dis 9:144. (PMID: 211720303022752)
Weisgraber KH, Rall SC Jr, Mahley RW (1981) Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J Biol Chem 256:9077–9083. (PMID: 7263700)
Wu L, Parhofer KG (2014) Diabetic dyslipidemia. Metabolism 63:1469–1479. (PMID: 25242435)
Zhao LL, Su G, Chen LX, Yan Q, Wang XP, Yuan W, Wang L, Zhang ZC (2017) Apolipoprotein E polymorphisms are associated with ischemic stroke susceptibility in a Northwest China Han population. Biosci Rep 37:BSR20171088.
Zhen J, Huang X, Van Halm-Lutterodt N, Dong S, Ma W, Xiao R, Yuan L (2017) ApoE rs429358 and rs7412 polymorphism and gender differences of serum lipid profile and cognition in aging Chinese population. Front Aging Neurosci 9:248. (PMID: 288244125539118)

Keywords: Apolipoprotein E (APOE); Korean population; Lipid profiles; Single nucleotide polymorphism (SNP); T2DM (type 2 diabetes mellitus)

0 (ApoE protein, human)
0 (Apolipoproteins E)
0 (Lipids)

Date Created: 20210417 Date Completed: 20220222 Latest Revision: 20220222

20221213

10.1007/s13258-021-01095-y

33864613