title: Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease.
abstract: The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a possible genetic link between CAD and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease.
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, 11211 Riyadh, Saudi Arabia.
authors.forename: Osama
authors.initials: O
authors.lastname: Alsmadi
authors.forename: Paul
authors.initials: P
authors.lastname: Muiya
authors.forename: Hanif
authors.initials: H
authors.lastname: Khalak
authors.forename: Haya
authors.initials: H
authors.lastname: Al-Saud
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.forename: Futwan
authors.initials: F
authors.lastname: Al-Mohanna
authors.forename: Maie
authors.initials: M
authors.lastname: Alshahid
authors.forename: Nduna
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D043262:Ribonuclease P / Q000235:genetics*
chemical_list: C545252:PRORP protein, human; D043262:Ribonuclease P; C465641:PSMA6 protein, human; D046988:Proteasome Endopeptidase Complex