title: Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population.
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.
authors.affiliation: Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), University of Dammam, P.O. Box 1982, 31441 Dammam, Saudi Arabia. asayed@uod.edu.sa.
authors.forename: Sayed
authors.initials: S
authors.lastname: AbdulAzeez
authors.affiliation: Department of Pathology, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. analnafie@uod.edu.sa.
authors.forename: Awatif N
authors.initials: AN
authors.lastname: Al-Nafie
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. ashehri60@yahoo.com.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Shehri
authors.affiliation: Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), University of Dammam, P.O. Box 1982, 31441 Dammam, Saudi Arabia. borgiomicro@gmail.com.
authors.forename: J Francis
authors.initials: JF
authors.lastname: Borgio
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, 3508 Utrecht, The Netherlands. E.V.Baranova@uu.nl.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Baranova
authors.affiliation: Department of Pediatrics, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. mmadan@uod.edu.sa.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Madan
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. rudaynahalali@hotmail.com.
authors.forename: Rudaynah A
authors.initials: RA
authors.lastname: Al-Ali
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. fmuhanna@uod.edu.sa.
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Muhanna
authors.affiliation: Department of Cardiology, King Fahd Hospital, Al-Hafof, 36441 Al-Ahssa, Saudi Arabia. qardoc@hotmail.com.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Ali
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. mmansori@uod.edu.sa.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Mansori
authors.affiliation: Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, 34445 Al-Khobar, Saudi Arabia. mfibrahim@uod.edu.sa.
authors.forename: Mohammed Fakhry
authors.initials: MF
authors.lastname: Ibrahim
authors.affiliation: Division of Heart &amp; Lungs, Department of Cardiology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands. F.W.Asselbergs@umcutrecht.nl.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, 19104 PA, USA. bkeating@mail.med.upenn.edu.
authors.forename: Brendan
authors.initials: B
authors.lastname: Keating
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, 3508 Utrecht, The Netherlands. B.P.C.Koeleman@umcutrecht.nl.
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.affiliation: Institute for Research and Medical Consultation (IRMC), University of Dammam, 31441 Dammam, Saudi Arabia. aalali@uod.edu.sa.
authors.forename: Amein K
authors.initials: AK
authors.lastname: Al-Ali
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D012529:Saudi Arabia
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding
keywords: CDKN2B-AS1 gene; Saudi Arabia; coronary artery disease; myocardial infarction; single nucleotide polymorphisms