Alsmadi Osama, Muiya Paul, Khalak Hanif, Al-Saud Haya, Meyer Brian F, Al-Mohanna Futwan, Alshahid Maie, Dzimiri Nduna
Genetics Department, King Faisal Specialist Hospital and Research Centre, 11211 Riyadh, Saudi Arabia.
Ann Hum Genet. 2009 Sep;73(Pt 5):475-83. doi: 10.1111/j.1469-1809.2009.00534.x. Epub 2009 Jun 16.
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.
KIAA0391和PSMA6基因在使个体易患疾病方面的作用仍未完全明确。我们通过基于分子信标的基因分型检测，评估了沙特人群中位于14q13.2染色体区域、包含KIAA0391和PSMA6基因簇的5个单核苷酸多态性（SNP）在冠状动脉疾病（CAD）中的作用。所研究的SNP中，rs8008319（记为1）和rs7157492（2）位于KIAA0391基因座，另外两个rs1048990（3）和rs12878391（4）是PSMA6的组成部分，而rs4981283（5）位于两个基因的下游。在一项涉及1071例患者和929例对照的研究中，所研究的SNP均未显示与CAD有显著关联。相反，在一个五SNP基因座模型中，由1A - 2G - 3C - 4A - 5A [优势比（95%可信区间）= 1.49(0.95 - 2.35)；p = 0.022]和1A - 2G - 3G - 4A - 5A [2.24(0.84 - 5.98)；p = 0.031]组成的两种单倍型赋予了CAD和心肌梗死（MI）风险，而另一种由1A - 2G - 3C - 4A - 5G [2.24(0.84 - 5.98)；p = 0.079]组成的单倍型显示出临界关联。由1T - 2G - 3C - 4G - 5A [0.79(0.59 - 1.05)；p = 0.015]组成的一种单倍型具有保护作用，另一种由1T - 2G - 3C - 4A - 5G [0.20(0.03 - 1.39)；p = 0.073]组成的单倍型显示出类似但较弱的趋势。我们的研究确定了包含KIAA0391和PSMA6基因的染色体区域中的单倍型是CAD和MI之间可能的遗传联系。这些结果还表明，在识别疾病风险因素方面，单倍型可能比单个SNP更具信息量。
