Abstract
Coronary artery disease (CAD) is an inflammatory heart disease characterized by the narrowing of coronary arteries. ATP-binding cassette transporter A1 (ABCA1) is a gene involved in regulation of cholesterol efflux and formation of high-density lipoprotein cholesterol (HDL-C). Present study aimed to explore the association of ABCA1 rs146292819 polymorphism with CAD development as well as its effect on serum lipid levels in the Pakistani population. Study subjects included 300 CAD patients and 300 age- and sex-matched healthy individuals. Methods involved genomic DNA extraction, amplification of rs146292819 polymorphism using allele-specific PCR, analyzing PCR product by agarose gel electrophoresis and determination of serum lipids. In this study, genotype frequencies of rs146292819 polymorphism in CAD patients were GG (43%), GT (27%), TT (30%) as compared to GG (25%), GT (31%), TT (44%) in healthy subjects. GG genotype increased the risk of developing CAD by 2.2326 times (OR 2.2326; 95% CI 1.5775–3.1597) and caused decrease in HDL-C levels by 2.6348 times. GT genotype was neither associated with CAD development (OR 0.8504; 95% CI 0.5974–1.2106) nor HDL-C levels. TT genotype lowered the risk of CAD development by 0.5381 times (OR 0.5381; 95% CI 0.3846–0.753) and protected from drop in HDL-C levels by 0.5086 times (OR 0.5086; 95% CI 0.3429–0.7544). It can be concluded that GG genotype of rs146292819 polymorphism and altered lipid profile act as risk factors in the pathogenesis of CAD in the Pakistani population.
Similar content being viewed by others
References
Attaur-Rasool S, Hasan S, Ghani N, Malik Z (2013) Pattern of conventional risk factors in coronary artery disease patients. Pak J Physiol 9:19–22
Attie AD, Kastelein JP, Hayden MR (2001) Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis. J Lipid Res 42:1717–1726
Bland JM, Altman DG (2000) The odds ratio. BMJ 320:1468
Bochem AE, Van Wijk DF, Holleboom AG, Duivenvoorden R, Motazacker MM, Dallinga-Thie GM, De Groot E, Kastelein JJ, Nederveen AJ, Hovingh GK, Stroes ES (2012) ABCA1 mutation carriers with low high-density lipoprotein cholesterol are characterized by a larger atherosclerotic burden. Eur Heart J 34:286–291
Çoban N, Onat A, Kömürcü-Bayrak E, Güleç Ç, Can G, Erginel-Ünaltuna N (2014) Gender specific association of ABCA1 gene R219K variant in coronary disease risk through interactions with serum triglyceride elevation in Turkish adults. Anadolu Kardiyol Derg 14:18–25
Colpo A (2005) LDL cholesterol: “bad” cholesterol or bad science? JPANDS 10:83–89
Daniels TF, Killinger KM, Michal JJ, Wright RW Jr, Jiang Z (2009) Lipoproteins, cholesterol homeostasis and cardiac health. Int J Biol Sci 5:474–488
Duarte PS, Mastrocolla LE, Alonso G, Lima EV, Smanio PE, Oliveira MA, Martins LR, Pereira JC (2007) Association between risk factors for coronary artery disease and coronary disease in patients undergoing myocardial perfusion scintigraphy. Arq Bras Cardiol 88:304–313
Frikke-Schmidt R, Nordestgaard BG, Jensen GB, Tybjærg-Hansen A (2004) Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population. J Clin Invest 114:1343–1353
Frikke-Schmidt R, Nordestgaard BG, Stene MC, Sethi AA, Remaley AT, Schnohr P, Grande P, Tybjærg-Hansen A (2008) Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA 299:2524–2532
Frikke-Schmidt R, Tybjærg-Hansen A, Dyson G, Haase CL, Benn M, Nordestgaard BG, Sing CF (2014) Subgroups at high risk for ischaemic heart disease: identification and validation in 67 000 individuals from the general population. Int J Epidemiol 44:117–128
Gupta N, Gill K, Singh S (2009) Paraoxonases: structure, gene polymorphism and role in coronary artery disease. Indian J Med Res 130:361–368
Haase CL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R (2015) High-density lipoprotein cholesterol and risk of type 2 diabetes: a Mendelian randomization study. Diabetes 64:3328–3333
Haghvirdizadeh P, Ramachandran V, Etemad A, Heidari F, Ghodsian N, Bin Ismail N, Ismail P (2015) Association of ATP-binding cassette transporter A1 gene polymorphisms in type 2 diabetes mellitus among Malaysians. J Diabetes Res 2015:289846
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695
Hussain M, Khan N, Uddin M, Al Nozha MM (2014) Chest pain, coronary artery disease and risk factors: a global snapshot. J Dow Univ Health Sci 8:80–86
Knoblauch H, Bauerfeind A, Toliat MR, Becker C, Luganskaja T, Günther UP, Rohde K, Schuster H, Junghans C, Luft FC, Nürnberg P (2004) Haplotypes and snps in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol. Hum Mol Genet 13:993–1004
Kolovou V, Marvaki A, Karakosta A, Vasilopoulos G, Kalogiani A, Mavrogeni S, Degiannis D, Marvaki C, Kolovou G (2012) Association of gender, ABCA1 gene polymorphisms and lipid profile in Greek young nurses. Lipids Health Dis 11:62
Nabel EG, Braunwald E (2012) A tale of coronary artery disease and myocardial infarction. N Engl J Med 366:54–63
Nordestgaard LT, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R (2015) Loss-of-function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease. Alzheimers Dement 11:1430–1438
Nordestgaard BG, Varbo A (2014) Triglycerides and cardiovascular disease. Lancet 384:626–635
Rader DJ, Alexander ET, Weibel GL, Billheimer J, Rothblat GH (2009) The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J Lipid Res 50:s189–s194
Rader DJ, Hovingh GK (2014) HDL and cardiovascular disease. Lancet 384:618–625
Rejeb J, Omezzine A, Rebhi L, Boumaiza I, Kchock K, Belkahla R, Rejeb NB, Nabli N, Abdelaziz AB, Boughzala E, Bouslama A (2010) Associations between common polymorphisms of adenosine triphosphate-binding cassette transporter A1 and coronary artery disease in a Tunisian population. Arch Cardiovasc Dis 103:530–537
Roberts R (2014) Acute coronary syndromes compendium genetics of coronary artery disease. Circ Res 114:1890–1903
Sakakura K, Nakano M, Otsuka F, Ladich E, Kolodgie FD, Virmani R (2013) Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ 22:399–411
Sayols-Baixeras S, Lluís-Ganella C, Lucas G, Elosua R (2014) Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants. Appl Clin Genet 7:15–32
Scheuner MT (2003) Genetic evaluation for coronary artery disease. Genet Med 5:269–285
Singaraja RR, Visscher H, James ER, Chroni A, Coutinho JM, Brunham LR, Kang MH, Zannis VI, Chimini G, Hayden MR (2006) Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitro. Circ Res 99:389–397
van Capelleveen JC, Kootte RS, Hovingh GK, Bochem AE (2015) Myocardial infarction in a 36-year-old man with combined ABCA1 and APOA-1 deficiency. J Clin Lipidol 9:396–399
Van Dam MJ, De Groot E, Clee SM, Hovingh GK, Roelants R, Brooks-Wilson A, Zwinderman AH, Smit AJ, Smelt AH, Groen AK, Hayden MR (2002) Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study. Lancet 359:37–41
Westerterp M, Bochem AE, Yvan-Charvet L, Murphy AJ, Wang N, Tall AR (2014) ATP-binding cassette transporters, atherosclerosis, and inflammation. Circ Res 114:157–170
Wong ND (2014) Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol 11:276–289
World Health Organization (2013) Country cooperation strategy at a glance: Pakistan. www.who.int/countryfocus/cooperation_strategy/briefs/en/. Accessed 22 Nov 2015
World Health Organization (2015) Cardiovascular diseases (CVDs) fact sheet. www.who.int/mediacentre/factsheets/fs317/en/. Accessed 6 Dec 2015
Acknowledgements
We are thankful to Department of Zoology, University of Sargodha, Sargodha, Pakistan, for providing well-equipped lab and facilitating us during research work.
Author information
Authors and Affiliations
Contributions
M.S. designed the study, performed lab work, statistically analyzed the data, and wrote the manuscript. A.R. helped in data collection and primer designing for PCR. M.A. edited the manuscript and approved the final manuscript for publication.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sameem, M., Rani, A. & Arshad, M. Association of rs146292819 Polymorphism in ABCA1 Gene with the Risk of Coronary Artery Disease in Pakistani Population. Biochem Genet 57, 623–637 (2019). https://doi.org/10.1007/s10528-019-09915-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-019-09915-3