Association of rs146292819 Polymorphism in ABCA1 Gene with the Risk of Coronary Artery Disease in Pakistani Population
- 30 Downloads
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.
KeywordsABCA1 gene rs146292819 polymorphism Coronary artery disease Cholesterol Polymerase chain reaction
We are thankful to Department of Zoology, University of Sargodha, Sargodha, Pakistan, for providing well-equipped lab and facilitating us during research work.
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.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Attaur-Rasool S, Hasan S, Ghani N, Malik Z (2013) Pattern of conventional risk factors in coronary artery disease patients. Pak J Physiol 9:19–22Google Scholar
- 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 42:1717–1726Google Scholar
- 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 34:286–291CrossRefGoogle Scholar
- 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 14:18–25Google Scholar
- Colpo A (2005) LDL cholesterol: “bad” cholesterol or bad science? JPANDS 10:83–89Google Scholar
- Gupta N, Gill K, Singh S (2009) Paraoxonases: structure, gene polymorphism and role in coronary artery disease. Indian J Med Res 130:361–368Google Scholar
- 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 2015:289846Google Scholar
- 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 8:80–86Google Scholar
- 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 13:993–1004CrossRefGoogle Scholar
- 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 103:530–537CrossRefGoogle Scholar
- 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 7:15–32Google Scholar
- 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 359:37–41CrossRefGoogle Scholar
- 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