Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Gene. 2012 Apr 25;498(1):13-9. doi: 10.1016/j.gene.2012.01.091. Epub 2012 Feb 4.
The paraoxonase (PON1) gene polymorphisms are known to affect the PON1 activity and coronary artery disease (CAD) risk. Studies done so far have given conflicting results. In the present study, we determined the role of PON1 genetic variants and PON1 activity in the development of CAD in North-West Indian Punjabis, a distinct ethnic group, having high incidence of both CAD and type 2 diabetes. 300 angiographically proven CAD with type 2 diabetics and 250 type 2 diabetics with no clinically evident CAD were enrolled. Serum PON1 activity and genotyping of coding (Q192R, L55M) and promoter (-909G/C, -162A/G, -108C/T) region polymorphisms were carried out and haplotypes were determined using PHASE software. The serum PON1 activity was significantly lower in CAD with type 2 diabetics as compared to diabetics alone (51.0 vs. 114.2nmol/min/ml). In logistic regression model after adjusting for confounding variables, lower PON1 activity was found to be significantly associated with CAD risk in type 2 diabetics with OR being 16.8 (95% CI: 10.2-27.7). The lower serum PON1 activity, irrespective of genotypes and haplotypes is a risk factor for development of CAD in North-West Indian Punjabis with type 2 diabetics.
对氧磷酶(PON1)基因多态性已知会影响 PON1 活性和冠心病(CAD)风险。迄今为止的研究结果存在矛盾。在本研究中,我们确定了 PON1 遗传变异和 PON1 活性在西北印度旁遮普邦人(一个具有高 CAD 和 2 型糖尿病发病率的独特族群)CAD 发展中的作用。我们招募了 300 名经血管造影证实的 CAD 合并 2 型糖尿病患者和 250 名无临床明显 CAD 的 2 型糖尿病患者。进行了血清 PON1 活性和编码(Q192R、L55M)和启动子(-909G/C、-162A/G、-108C/T)区域多态性的基因分型,并使用 PHASE 软件确定了单倍型。与单纯糖尿病患者相比,CAD 合并 2 型糖尿病患者的血清 PON1 活性显着降低(51.0 与 114.2nmol/min/ml)。在调整混杂变量的逻辑回归模型中,发现较低的 PON1 活性与 2 型糖尿病患者的 CAD 风险显着相关,OR 为 16.8(95%CI:10.2-27.7)。无论基因型和单倍型如何,较低的血清 PON1 活性都是西北印度旁遮普邦 2 型糖尿病患者发生 CAD 的危险因素。