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Int. J. Mol. Sci. 2016, 17(3), 395; doi:10.3390/ijms17030395

Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

1
Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), University of Dammam, P.O. Box 1982, 31441 Dammam, Saudi Arabia
2
Department of Pathology, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia
3
Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia
4
Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, 3508 Utrecht, The Netherlands
5
Department of Pediatrics, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia
6
Department of Cardiology, King Fahd Hospital, Al-Hafof, 36441 Al-Ahssa, Saudi Arabia
7
Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
8
Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, 19104 PA, USA
9
Department of Medical Genetics, University Medical Center Utrecht, 3508 Utrecht, The Netherlands
10
Institute for Research and Medical Consultation (IRMC), University of Dammam, 31441 Dammam, Saudi Arabia
*
Author to whom correspondence should be addressed.
Academic Editor: Emil Alexov
Received: 8 February 2016 / Revised: 2 March 2016 / Accepted: 11 March 2016 / Published: 17 March 2016
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
View Full-Text   |   Download PDF [2836 KB, uploaded 17 March 2016]   |  

Abstract

Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs) on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease) in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI) and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD) = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2). The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175) and a risk haplotype (TGGA p = 2.86 × 10 − 10) for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD. View Full-Text
Keywords: coronary artery disease; myocardial infarction; single nucleotide polymorphisms; CDKN2B-AS1 gene; Saudi Arabia coronary artery disease; myocardial infarction; single nucleotide polymorphisms; CDKN2B-AS1 gene; Saudi Arabia
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AbdulAzeez, S.; Al-Nafie, A.N.; Al-Shehri, A.; Borgio, J.F.; Baranova, E.V.; Al-Madan, M.S.; Al-Ali, R.A.; Al-Muhanna, F.; Al-Ali, A.; Al-Mansori, M.; Ibrahim, M.F.; Asselbergs, F.W.; Keating, B.; Koeleman, B.P.C.; Al-Ali, A.K. Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population. Int. J. Mol. Sci. 2016, 17, 395.

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