Çakmak Hüseyin Altuğ, Bayoğlu Burcu, Durmaz Eser, Can Günay, Karadağ Bilgehan, Cengiz Müjgan, Vural Vural Ali, Yüksel Hüsniye
Department of Cardiology, Cerrahpaşa Medical Faculty, İstanbul University; İstanbul-Turkey.
Anatol J Cardiol. 2015 Mar;15(3):196-203. doi: 10.5152/akd.2014.5285. Epub 2014 Apr 8.
Coronary artery disease (CAD), which develops from complex interactions between genetic and enviromental factors, is a leading cause of death worldwide. Based on genome-wide association studies (GWAS), the chromosomal region 9p21 has been identified as the most relevant locus presenting a strong association with CAD in different populations. The aim of the present study was to investigate the association of two SNPs on chromosome 9p21 on susceptibility to CAD and the effect of these SNPs along with cardiovascular risk factors on the severity of CAD in the Turkish population.
This study had an observational case-control design. We genotyped 460 subjects, aged 30-65 years, to investigate the association of 2 SNPs (rs1333049, rs2383207) on chromosome 9p21 and CAD risk in Turkish population. Real-time polymerase chain reaction (RT-PCR) was used to analyze the 2 SNPs in CAD patients and healthy controls. The genotype and allelic variations of these SNPs with the severity of CAD was also assessed using semi-quantitative methods such as the Gensini score. Student's t test and multiple regression analysis were used for statistical analysis.
The SNPs rs1333049 and rs2383207 were found to be associated with CAD with an adjusted OR of 1.81 (95% Cl 1.05-3.12) and 2.12 (95% CI 1.19-4.10) respectively. After adjustment of CAD risk factors such as smoking, family history of CAD and diabetes, the homozygous AA genotype for rs2383207 increased the CAD risk with an OR 3.69. Also a very strong association was found between rs1333049 and rs2383207 and Gensini scores representing the severity of CAD (p<0.001).
The rs2383207 and rs1333049 SNPs on 9p21 chromosome were significantly associated with the risk and severity of CAD in the Turkish population.
冠状动脉疾病（CAD）是全球主要的死亡原因之一，它由遗传和环境因素之间的复杂相互作用发展而来。基于全基因组关联研究（GWAS），9号染色体短臂21区（9p21）已被确定为在不同人群中与CAD关联最为密切的位点。本研究旨在探讨9号染色体上两个单核苷酸多态性（SNP）与土耳其人群CAD易感性的关联，以及这些SNP与心血管危险因素对CAD严重程度的影响。
本研究采用观察性病例对照设计。我们对460名年龄在30 - 65岁之间的受试者进行基因分型，以研究9号染色体上两个SNP（rs1333049、rs2383207）与土耳其人群CAD风险的关联。采用实时聚合酶链反应（RT-PCR）分析CAD患者和健康对照中的这两个SNP。还使用半定量方法如Gensini评分评估这些SNP的基因型和等位基因变异与CAD严重程度的关系。采用学生t检验和多元回归分析进行统计分析。
发现SNP rs1333049和rs2383207与CAD相关，校正后的比值比（OR）分别为1.81（95%可信区间[CI] 1.05 - 3.12）和2.12（95% CI 1.19 - 4.10）。在调整吸烟、CAD家族史和糖尿病等CAD危险因素后，rs2383207的纯合子AA基因型使CAD风险增加，OR为3.69。此外，还发现rs1333049和rs2383207与代表CAD严重程度的Gensini评分之间存在非常强的关联（p<0.001）。
9号染色体上的rs2383207和rs1333049 SNP与土耳其人群CAD的风险和严重程度显著相关。
