College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
Gene. 2018 Oct 5;673:206-210. doi: 10.1016/j.gene.2018.06.024. Epub 2018 Jun 9.
Genome-wide association studies (GWASs) have yielded a wealth of information furnishing support for the variability in genetic predisposition to disease. However, the actual impact of such findings on any particular ethnic population needs to be validated through replication studies. In the present study, we verified recent findings of a GWAS demonstrating a strong association for the cyclin-dependent kinase 4 inhibitor B (CDKN2B) genomic region with coronary artery disease (CAD)/myocardial infarction (MI) in ethnic Saudi Arabs.
We genotyped 8 CDKN2B SNPs for cardiovascular risk in 4650 Saudi Arabs, comprising 2429 CAD cases (1860 males; 569 female) and 2221 controls (1189 male; 1032 female) by Taqman assay.
Four SNPs, rs4977574_A [0.56(0.50-0.63); p < 0.0001], rs10757274_A [0.87(0.77-0.97); p = 0.014], rs10738607_A [0.89(0.80-1.00); p = 0.043] and rs1333045_T [0.54(0.48-0.61); p < 0.0001] residing on the CDKN2B gene were significantly associated with CAD following multivariate adjustments for MI, HTN and DM, while four others were weakly associated with the disease. Likewise, three SNPs, rs1412829_G [0.84(0.72-0.97); p = 0.019], rs564398_C [0.81(0.70-0.94); p = 0.006], rs4977756_G [0.87(0.76-0.99); p = 0.036] were significantly associated with MI after multivariate adjustments for CAD, HTN and DM, while the other five displayed borderline associations.
Our findings strongly support the notion of a critical role for the CDKN2B gene locus as a cardiovascular risk in ethnic Arabs. The study also demonstrates the importance of replication studies in ascertaining the role of a genomic sequence in disease.
全基因组关联研究（GWAS）提供了大量信息，为疾病遗传易感性的变异提供了支持。然而，这些发现对任何特定种族群体的实际影响都需要通过复制研究来验证。在本研究中，我们验证了最近一项 GWAS 的发现，该研究表明细胞周期蛋白依赖性激酶 4 抑制剂 B（CDKN2B）基因区域与沙特阿拉伯种族的冠状动脉疾病（CAD）/心肌梗死（MI）之间存在强烈关联。
我们通过 Taqman 分析对 4650 名沙特阿拉伯人进行了 8 个 CDKN2B 单核苷酸多态性（SNP）的心血管风险基因分型，其中包括 2429 名 CAD 病例（1860 名男性；569 名女性）和 2221 名对照（1189 名男性；1032 名女性）。
四个 SNP，rs4977574_A [0.56(0.50-0.63); p < 0.0001]，rs10757274_A [0.87(0.77-0.97); p = 0.014]，rs10738607_A [0.89(0.80-1.00); p = 0.043]和 rs1333045_T [0.54(0.48-0.61); p < 0.0001] 位于 CDKN2B 基因上，与多变量调整后的 CAD 显著相关，包括 MI、HTN 和 DM，而另外四个 SNP 与疾病呈弱相关。同样，三个 SNP，rs1412829_G [0.84(0.72-0.97); p = 0.019]，rs564398_C [0.81(0.70-0.94); p = 0.006]，rs4977756_G [0.87(0.76-0.99); p = 0.036]与多变量调整后的 CAD、HTN 和 DM 显著相关，而另外五个 SNP 则呈边缘相关。
我们的研究结果强烈支持 CDKN2B 基因座作为阿拉伯种族心血管风险的关键作用的观点。该研究还表明，复制研究在确定基因组序列在疾病中的作用方面非常重要。
