Apolipoprotein C3 genetic polymorphisms are associated with lipids and coronary artery disease in a Chinese population

Lipids in Health and Disease

ChangShan An⁴  XueWu Zhang³  YunFeng Li²  KeZhong Li¹  FengHe Cui¹ 

[1] Department of Anesthesiology, Yantai Yuhuangding Hospital, Yantai 264000, China;Department of Anesthesiology, Weihai Municipal Hospital, Weihai 264200, China;Department of Biochemistry and Molecular Biology, Basic College of Yanbian University, Yanji 133000, China;Department of Respiratory Medicine, Clinical College of Yanbian University, No. 1327 Juzi Street, Yanji 133000, China

关键词: Coronary artery disease;    Lipid;    Gene polymorphism;    Apolipoprotein C3;   

Others  :  1145607
DOI  :  10.1186/1476-511X-13-170

 received in 2014-10-06, accepted in 2014-10-23,  发布年份 2014

【 摘 要 】

Background

The disorder of triglyceride (TG) metabolism leading to hypertriglyceridemia is an independent risk factor for coronary artery disease (CAD). Variants in the apolipoprotein C3 (APOC3) gene were found to be associated with elevated TG levels. The purpose of this study was to investigate the effect of two polymorphisms (1100 C/T and 3238 C/G) of APOC3 on plasma lipid and risk of CAD in a Chinese population.

Methods

The study population consisted of 600 patients with CAD and 600 age- and gender-matched controls. The APOC3 gene polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

Patients with CAD had a significantly higher frequency of APOC3 3238 GG genotype [odds ratio (OR) =1.64, 95% confidence interval (CI) =1.10, 2.43; P = 0.01] and APOC3 3238 G allele (OR =1.27, 95% CI =1.04, 1.55; P = 0.02) than controls. The findings are still emphatic by the Bonferroni correction. When stratifying by hyperlipidemia, CAD patients with hyperlipidemia had a significantly higher frequency of APOC3 3238 GG genotype (OR =1.73, 95% CI =1.13, 2.64; P = 0.01) than without hyperlipidemia. The APOC3 3238 G allele was significantly associated with increasing plasma TG levels and very-low-density lipoprotein cholesterol (VLDL-C) levels both in cases and controls (P < 0.001).

Conclusions

The APOC3 3238 G allele might contribute to an increased risk of CAD as a result of its effect on TG and VLDL-C metabolism.

【 授权许可】

   
2014 Cui et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Negi S, Anand A: Atherosclerotic coronary heart disease-epidemiology, classification and management. Cardiovasc Hematol Disord Drug Targets 2010, 10:257-261.
• [2]Bowron A, Scott J, Stansbie D: The influence of genetic and environmental factors on plasma homocysteine concentrations in a population at high risk for coronary artery disease. Ann Clin Biochem 2005, 42:459-462.
• [3]Hrira MY, Chkioua L, Slimani A, Chahed H, Mosbah H, Khaldoun HB, Ferchichi S, Addad F, Miled A: Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease. Diagn Pathol 2012, 7:88. BioMed Central Full Text
• [4]Maouche S, Schunkert H: Strategies beyond genome-wide association studies for atherosclerosis. Arterioscler Thromb Vasc Biol 2012, 32:170-181.
• [5]Roberts R, Stewart AF: Genes and coronary artery disease: where are we? J Am Coll Cardiol 2012, 60:1715-1721.
• [6]Adi D, Xie X, Ma YT, Fu ZY, Yang YN, Li XM, Xiang Y, Liu F, Chen BD: Association of COL4A1 genetic polymorphisms with coronary artery disease in Uygur population in Xinjiang. China Lipids Health Dis 2013, 12:153. BioMed Central Full Text
• [7]Roberts R, Stewart AF: The genetics of coronary artery disease. Curr Opin Cardiol 2012, 27:221-227.
• [8]O'Donnell CJ, Kavousi M, Smith AV, Kardia SL, Feitosa MF, Hwang SJ, Sun YV, Province MA, Aspelund T, Dehghan A, Hoffmann U, Bielak LF, Zhang Q, Eiriksdottir G, van Duijn CM, Fox CS, de Andrade M, Kraja AT, Sigurdsson S, Elias-Smale SE, Murabito JM, Launer LJ, van der Lugt A, Kathiresan S, Consortium CA, Krestin GP, Herrington DM, Howard TD, Liu Y, Post W, et al.: Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation 2011, 124:2855-2864.
• [9]Mehta NN: Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Circ Cardiovasc Genet 2011, 4:327-329.
• [10]Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, Absher D, Aherrahrou Z, Allayee H, Altshuler D, Anand SS, Andersen K, Anderson JL, Ardissino D, Ball SG, Balmforth AJ, Barnes TA, Becker DM, Becker LC, Berger K, Bis JC, Boekholdt SM, Boerwinkle E, Braund PS, Brown MJ, Burnett MS, et al.: Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 2011, 43:333-338.
• [11]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.
• [12]Masebe T, Bessong PO, Ndip RN, Meyer D: Genetic variants of APOC3 promoter and HLA-B genes in an HIV infected cohort in northern South Africa: a pilot study. Int J Mol Sci 2014, 15:11403-11415.
• [13]Tarr PE, Taffe P, Bleiber G, Furrer H, Rotger M, Martinez R, Hirschel B, Battegay M, Weber R, Vernazza P, Bernasconi E, Darioli R, Rickenbach M, Ledergerber B, Telenti A, Swiss HIVCS: Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. J Infect Dis 2005, 191:1419-1426.
• [14]Lin B, Huang Y, Zhang M, Wang J, Wu Y: Association between apolipoprotein C3 Sst I, T-455C, C-482T and C1100T polymorphisms and risk of coronary heart disease. BMJ Open 2014, 4:e004156.
• [15]Fiegenbaum M, de Andrade FM, Hutz MH: Association between plasma lipid parameters and APOC3 genotypes in Brazilian subjects: effect of gender, smoking and APOE genotypes. Clin Chim Acta 2007, 380:175-181.
• [16]Shoulders CC, Harry PJ, Lagrost L, White SE, Shah NF, North JD, Gilligan M, Gambert P, Ball MJ: Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII. Atherosclerosis 1991, 87:239-247.
• [17]Bhanushali AA, Das BR: Influence of genetic variants in the apolipoprotein A5 and C3 gene on lipids, lipoproteins, and its association with coronary artery disease in Indians. J Community Genet 2010, 1:139-148.
• [18]AshokKumar M, Subhashini NG, SaiBabu R, Ramesh A, Cherian KM, Emmanuel C: Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians. Mol Biol Rep 2010, 37:521-527.
• [19]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. BioMed Central Full Text
• [20]Waterworth DM, Ribalta J, Nicaud V, Dallongeville J, Humphries SE, Talmud P: ApoCIII gene variants modulate postprandial response to both glucose and fat tolerance tests. Circulation 1999, 99:1872-1877.
• [21]Chakravarti A, Buetow KH, Antonarakis SE, Waber PG, Boehm CD, Kazazian HH: Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet 1984, 36:1239-1258.
• [22]Gu JY, Li LW: ALDH2 Glu504Lys polymorphism and susceptibility to coronary artery disease and myocardial infarction in East Asians: a meta-analysis. Arch Med Res 2014, 45:76-83.
• [23]Zhang FX, Sun DP, Guan N, Chen JJ, Huo XC, Luo JS: Association between -1562C>T polymorphism in the promoter region of matrix metalloproteinase-9 and coronary artery disease: a meta-analysis. Genet Test Mol Biomarkers 2014, 18:98-105.
• [24]Li Y, Li X, Jia N, Guo S, Chu S, Niu W: Meta-analysis of the association between angiotensin II receptor, type 1 gene A1166C polymorphism and coronary artery disease in Chinese populations. J Renin Angiotensin Aldosterone Syst 2013, 14:82-90.
• [25]Wang Z, Yang Y, He M, Wang R, Ma J, Zhang Y, Zhao L, Yu K: Association between interleukin-6 gene polymorphisms and bone mineral density: a meta-analysis. Genet Test Mol Biomarkers 2013, 17:898-909.
• [26]Xuan CL, Yan W, Xuan L, Xu RH: PTGS2 gene polymorphism -765G>C is associated with coronary artery disease: a meta-analysis. Genet Mol Res 2014, 13:1491-1496.
• [27]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
• [28]Wu Z, Lou Y, Jin W, Liu Y, Lu L, Chen Q, Zhang R: The Connexin37 gene C1019T polymorphism and risk of coronary artery disease: a meta-analysis. Arch Med Res 2014, 45:21-30.
• [29]Wang H, Fu Y, Liu D, Zhang M, Zhang G, Wu W, Yang S, Li C, Zhang H: The COX-2 rs20417 polymorphism and risk of coronary artery disease: evidence from 17,621 subjects. Heart Lung Circ 2014, 23:572-577.
• [30]Zhou YF, Zhang J, Li ZX, Miao JL, Yin QX, Li JJ, Zhang XY, Li YY, Luo HL: Association of liver X receptor alpha (LXRalpha) gene polymorphism and coronary heart disease, serum lipids and glucose levels. Lipids Health Dis 2014, 13:34. BioMed Central Full Text
• [31]Yin YW, Sun QQ, Zhang BB, Hu AM, Liu HL, Wang Q, Hou ZZ: Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Chinese population: evidence from a meta-analysis of 40 studies. PLoS One 2013, 8:e66924.
• [32]Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM, Dziura J, Lifton RP, Shulman GI: Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010, 362:1082-1089.
• [33]Dorfmeister B, Cooper JA, Stephens JW, Ireland H, Hurel SJ, Humphries SE, Talmud PJ: The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes. Biochim Biophys Acta 2007, 1772:355-363.
• [34]van Hoek M, van Herpt TW, Dehghan A, Hofman A, Lieverse AG, van Duijn CM, Witteman JC, Sijbrands EJ: Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons. Diabetologia 2011, 54:1360-1367.
• [35]Ding Y, Zhu MA, Wang ZX, Zhu J, Feng JB, Li DS: Associations of polymorphisms in the apolipoprotein APOA1-C3-A5 gene cluster with acute coronary syndrome. J Biomed Biotechnol 2012, 2012:509420.
• [36]Coban N, Onat A, Guclu-Geyik F, Komurcu-Bayrak E, Sansoy V, Hergenc G, Can G, Erginel-Unaltuna N: Gender- and obesity-specific effect of apolipoprotein C3 gene (APOC3) -482C>T polymorphism on triglyceride concentration in Turkish adults. Clin Chem Lab Med 2012, 50:285-292.
• [37]Baum L, Ng MC, So WY, Lam VK, Wang Y, Poon E, Tomlinson B, Cheng S, Lindpaintner K, Chan JC: Effect of hepatic lipase -514C->T polymorphism and its interactions with apolipoprotein C3–482C->T and apolipoprotein E exon 4 polymorphisms on the risk of nephropathy in chinese type 2 diabetic patients. Diabetes Care 2005, 28:1704-1709.
• [38]Sun Y, Shi J, Zhang S, Tang M, Han H, Guo Y, Ma C, Liu X, Li T: The APOC3 SstI polymorphism is weakly associated with sporadic Alzheimer's disease in a Chinese population. Neurosci Lett 2005, 380:219-222.
• [39]Miller M, Rhyne J, Chen H, Beach V, Ericson R, Luthra K, Dwivedi M, Misra A: APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome. Arch Med Res 2007, 38:444-451.
• [40]Pollex RL, Ban MR, Young TK, Bjerregaard P, Anand SS, Yusuf S, Zinman B, Harris SB, Hanley AJ, Connelly PW, Huff MW, Hegele RA: Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample. BMC Med Genet 2007, 8:80.
• [41]Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V: Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007, 115:450-458.
• [42]Hallman DM, Srinivasan SR, Chen W, Boerwinkle E, Berenson GS: Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study. Metabolism 2006, 55:1574-1581.