Effect of apolipoprotein A1 genetic polymorphisms on lipid profiles and the risk of coronary artery disease

Diagnostic Pathology

ZhengLei Xu²  HuaDong Liu¹  ShaoHong Dong¹  KeQi Cheng¹  BiHong Liao¹ 

[1] Department of Cardiology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen 518000, Guangdong Province, China;Department of Internal Medicine, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, NO. 1017 East Gate Road, Shenzhen 518000, Guangdong Province, China

关键词: Lipid;    Coronary artery disease;    Gene polymorphism;    Apolipoprotein A1;   

Others  :  1219329
DOI  :  10.1186/s13000-015-0328-7

 received in 2015-03-12, accepted in 2015-06-12,  发布年份 2015

【 摘 要 】

Background

The disorder of lipid metabolism and genetic predisposition are major risk factors for coronary artery disease (CAD). Variants in the apolipoprotein A1 (APOA1) gene play an important role in the regulation of lipids. The objective of the present study was to investigate the effect of two polymorphisms (-75 G/A and +83 C/T) of APOA1 on lipid profiles and the risk of CAD.

Methods

A total number of 300 subjects with CAD and 300 age and sex matched healthy controls were enrolled for the study. Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing.

Results

The frequencies of APOA1 -75 AA genotype [odds ratio (OR) =0.50, 95 % confidence interval (CI) = 0.28, 0.88; P = 0.02] and APOA1 -75 A allele (OR =0.76, 95 % CI = 0.59, 0.98; P = 0.04) were significantly lower in CAD than in controls. The APOA1 -75 A allele was significantly associated with increasing serum concentrations of ApoA1 and high-density lipoprotein cholesterol (HDL-C) (P < 0.001).

Conclusions

The individuals with the APOA1 -75 A allele were likely to have a lower risk of CAD as a result of its effect on higher serum concentrations of ApoA1 and HDL-C.

【 授权许可】

   
2015 Liao et al.

【 参考文献 】

• [1]Ordovas JM, Schaefer EJ. Coronary artery disease, lipid disorders and genetic polymorphisms. Ann Biol Clin (Paris). 1988; 46:24-29.
• [2]Zou JG, Ma YT, Xie X, Yang YN, Pan S, Adi D, Liu F, Chen BD. The association between CYP1A1 genetic polymorphisms and coronary artery disease in the Uygur and Han of China. Lipids Health Dis. 2014;13:145.
• [3]Schaefer LE, Nechemias C. Endogenous Hormones, Lipid Metabolism, and Coronary Artery Disease. Prog Cardiovasc Dis. 1965; 7:449-464.
• [4]van Hateren KJ, Bilo HJ. Hypertension control and cardiovascular outcomes among patients with diabetes and coronary artery disease. JAMA. 2010; 304:1672.
• [5]Dunn JP, Ipsen J, Elsom KO, Ohtani M. Risk factors in coronary artery disease, hypertension and diabetes. Am J Med Sci. 1970; 259:309-322.
• [6]Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316:823–8.
• [7]Connelly PW, Stachenko S, MacLean DR, Petrasovits A, Little JA. The prevalence of hyperlipidemia in women and its association with use of oral contraceptives, sex hormone replacement therapy and nonlipid coronary artery disease risk factors. Canadian Heart Health Surveys Research Group. Can J Cardiol. 1999; 15:419-427.
• [8]Li XL, Hong LF, Luo SH, Guo YL, Zhu CG, Sun J, Dong Q, Qing P, Xu RX, Liu J, et al. Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease. Lipids Health Dis. 2014;13:73.
• [9]Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Shindo T, Minamino T, Ohno M, et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation. 1997;95:2032–6.
• [10]Neutze J, Cormack B, Kerr B, Pepper L, Ramage C. Contribution of a risk factor clinic to lipid management in patients with coronary artery disease. N Z Med J. 1992; 105:97-99.
• [11]Gruzdeva O, Uchasova E, Dyleva Y, Belik E, Karetnikova V, Shilov A, Barbarash O. Multivessel coronary artery disease, free fatty acids, oxidized LDL and its antibody in myocardial infarction. Lipids Health Dis. 2014;13:111.
• [12]Kraus WE. Genetic approaches for the investigation of genes associated with coronary heart disease. Am Heart J. 2000; 140:S27-35.
• [13]Verdoia M, Cassetti E, Schaffer A, Di Giovine G, De Luca G: Platelet glycoprotein IIIa Leu33Pro gene polymorphism and coronary artery disease: A meta-analysis of cohort studies. Platelets 2014:1-6. doi:. 10. 3109/09537104.2014.948839
• [14]Zhang Z, Chu G, Yin RX. Apolipoprotein M T-778C polymorphism is associated with serum lipid levels and the risk of coronary artery disease in the Chinese population: a meta-analysis. Lipids Health Dis. 2013; 12:135. BioMed Central Full Text
• [15]Segrest JP, Li L, Anantharamaiah GM, Harvey SC, Liadaki KN, Zannis V. Structure and function of apolipoprotein A-I and high-density lipoprotein. Curr Opin Lipidol. 2000; 11:105-115.
• [16]Karathanasis SK. Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci U S A. 1985; 82:6374-6378.
• [17]Saha N, Tay JS, Low PS, Humphries SE. Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in Chinese non-smokers. Genet Epidemiol. 1994; 11:255-264.
• [18]Wang XL, Badenhop R, Humphrey KE, Wilcken DE. New MspI polymorphism at +83 bp of the human apolipoprotein AI gene: association with increased circulating high density lipoprotein cholesterol levels. Genet Epidemiol. 1996; 13:1-10.
• [19]Dawar R, Gurtoo A, Singh R. Apolipoprotein A1 gene polymorphism (G-75A and C + 83 T) in patients with myocardial infarction: a pilot study in a north Indian population. Am J Clin Pathol. 2010; 134:249-255.
• [20]Rai TS, Khullar M, Sehrawat BS, Ahuja M, Sharma PK, Vijayvergiya R, Grover A. Synergistic effect between apolipoprotein E and apolipoprotein A1 gene polymorphisms in the risk for coronary artery disease. Mol Cell Biochem. 2008;313:139–46.
• [21]Shanker J, Perumal G, Rao VS, Khadrinarasimhiah NB, John S, Hebbagodi S, Mukherjee M, Kakkar VV. Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease. Lipids Health Dis. 2008;7:33.
• [22]Zou Y, Hu D, Yang X, Jia X, Wang L, Cui L, Liu X, Gao M, Wei Y, Xu Z. Relationships among apolipoprotein A1 gene polymorphisms, lipid levels and coronary atherosclerosis disease. Chin Med J (Engl). 2003;116:665–8.
• [23]Wang H, Dong P. Thrombomodulin -33G/A and Ala455Val polymorphisms are associated with the risk of coronary artery disease: a meta-analysis including 12 584 patients. Coron Artery Dis. 2015; 26:72-77.
• [24]Zhang S, Zhang Z, Zhang F, Wei C, Bu Y, Zheng S, Su D. Association between thrombomodulin polymorphisms and coronary artery disease risk: a meta-analysis. Med Sci Monit. 2014;20:1407–12.
• [25]Zhang H, Dong P, Yang X, Liu Z. Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with coronary artery disease risk: a meta-analysis. Int J Clin Exp Med. 2014; 7:3777-3788.
• [26]Yang Y, Du K, Liu Z, Lu X. Endothelial nitric oxide synthase (eNOS) 4b/a gene polymorphisms and coronary artery disease: evidence from a meta-analysis. Int J Mol Sci. 2014; 15:7987-8003.
• [27]Xu Q, Yuan F, Shen X, Wen H, Li W, Cheng B, Wu J. Polymorphisms of C242T and A640G in CYBA gene and the risk of coronary artery disease: a meta-analysis. PLoS One. 2014;9:e84251.
• [28]Wu Z, Lou Y, Lu L, Liu Y, Chen Q, Chen X, Jin W. Heterogeneous effect of two selectin gene polymorphisms on coronary artery disease risk: a meta-analysis. PLoS One. 2014;9:e88152.
• [29]Li D, Qu C, Dong P. The ICAM-1 K469E polymorphism is associated with the risk of coronary artery disease: a meta-analysis. Coron Artery Dis. 2014; 25:665-670.
• [30]Chiodini BD, Barlera S, Franzosi MG, Beceiro VL, Introna M, Tognoni G. APO B gene polymorphisms and coronary artery disease: a meta-analysis. Atherosclerosis. 2003; 167:355-366.
• [31]Tu J, Zhang B, Chen Y, Liang B, Liang D, Liu G, He F. Association of apolipoprotein A1–75 G/A polymorphism with susceptibility to the development of acute lung injury after cardiopulmonary bypass surgery. Lipids Health Dis. 2013;12:172.
• [32]Koutsis G, Panas M, Giogkaraki E, Karadima G, Sfagos C, Vassilopoulos D. An APOA1 promoter polymorphism is associated with cognitive performance in patients with multiple sclerosis. Mult Scler. 2009; 15:174-179.
• [33]Hamrita B, Ben Nasr H, Gabbouj S, Bouaouina N, Chouchane L, Chahed K. Apolipoprotein A1–75 G/A and +83 C/T polymorphisms: susceptibility and prognostic implications in breast cancer. Mol Biol Rep. 2011;38:1637–43.
• [34]Vollbach H, Heun R, Morris CM, Edwardson JA, McKeith IG, Jessen F, Schulz A, Maier W, Kolsch H. APOA1 polymorphism influences risk for early-onset nonfamiliar AD. Ann Neurol. 2005;58:436–41.
• [35]Chen ES, Mazzotti DR, Furuya TK, Cendoroglo MS, Ramos LR, Araujo LQ, Burbano RR, de Arruda Cardoso Smith M. Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity. Clin Exp Med. 2009;9:319–25.
• [36]Dixit M, Choudhuri G, Saxena R, Mittal B. Association of apolipoprotein A1-C3 gene cluster polymorphisms with gallstone disease. Can J Gastroenterol. 2007; 21:569-575.
• [37]Barre DE, Guerra R, Verstraete R, Wang Z, Grundy SM, Cohen JC. Genetic analysis of a polymorphism in the human apolipoprotein A-I gene promoter: effect on plasma HDL-cholesterol levels. J Lipid Res. 1994; 35:1292-1296.
• [38]Civeira F, Pocovi M, Cenarro A, Garces C, Ordovas JM. Adenine for guanine substitution -78 base pairs 5' to the apolipoprotein (APO) A-I gene: relation with high density lipoprotein cholesterol and APO A-I concentrations. Clin Genet. 1993; 44:307-312.
• [39]Wang XL, Liu SX, McCredie RM, Wilcken DE. Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of coronary artery disease. J Clin Invest. 1996; 98:372-377.
• [40]Jeenah M, Kessling A, Miller N, Humphries S. G to A substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI and high density lipoprotein cholesterol concentrations. Mol Biol Med. 1990; 7:233-241.
• [41]Meng QH, Pajukanta P, Valsta L, Aro A, Pietinen P, Tikkanen MJ. Influence of apolipoprotein A-1 promoter polymorphism on lipid levels and responses to dietary change in Finnish adults. J Intern Med. 1997; 241:373-378.
• [42]Pagani F, Sidoli A, Giudici GA, Barenghi L, Vergani C, Baralle FE. Human apolipoprotein A-I gene promoter polymorphism: association with hyperalphalipoproteinemia. J Lipid Res. 1990; 31:1371-1377.
• [43]Paul-Hayase H, Rosseneu M, Robinson D, Van Bervliet JP, Deslypere JP, Humphries SE. Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations. Hum Genet. 1992; 88:439-446.
• [44]Xu CF, Angelico F, Del Ben M, Humphries S. Role of genetic variation at the apo AI-CIII-AIV gene cluster in determining plasma apo AI levels in boys and girls. Genet Epidemiol. 1993; 10:113-122.