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The KIAA0391 and PSMA6 gene cluster confers a risk factor for coronary artery disease
Author(s) -
Dzimiri Nduna,
Muiya Paul,
Alsmadi Osma,
AlSaud Haya,
Meyer Brian,
Alshahid Maie,
AlMohanna Futwan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.573.2
Subject(s) - haplotype , coronary artery disease , single nucleotide polymorphism , genotyping , medicine , locus (genetics) , snp , risk factor , case control study , gastroenterology , population , biology , genetics , gene , genotype , environmental health
We evaluated by molecular beacon‐based genotyping assays the roles of 5 SNPs in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. In a preliminary study involving 502 patients and 474 controls, we depicted rs4981283 (denoted as 5) (χ 2 =0.014; p=0.015) as conferring risk for CAD and the rs7157492 (2) (χ 2 =0.027; p=0.028) as protective, while the rs8008319 (1) (χ 2 =0.045; p=0.055), rs1048990 (3) and rs1287391 (4) were not associated with CAD. Increasing the study size to 1166 patients and 835 controls resulted in the diminishing of the significance for these associations. In contrast, 3 haplotypes consisting of 1T‐2G‐3C‐4G‐5A (χ 2 =9.99, p<0.0001), 1T‐2A‐3G‐4A‐5G (χ 2 = 7.80, p<0.03) and 1A‐2A‐3G‐4G‐5A (χ 2 =6.93, p<0.03) with frequency of 0.042, 0.010 and 0.001 respectively in controls consistently conferred risk for CAD in a 5‐SNP locus model in both the preliminary and primary studies. Two other haplotypes [1A‐2G‐3G‐4A‐5A (χ 2 =6.15, p<0.04) and 1T‐2A‐3G‐4G‐5A (χ 2 =8.2, p<0.04)] with frequencies of 0.01 and 0.003 respectively in the controls, were protective. Notably, the haplotype 1T‐2G‐2C‐4G‐5A also conferred risk for MI (χ 2 =4.91, p<0.05). Thus, our study identified a haplotype in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a genetic link between CAD and MI, and points to haplotypes as more informative markers than individual SNPs for identifying disease risk factors.