Kaur Naindeep, Singh Jagtar, Reddy S
Department of Biotechnology, Panjab University, Chandigarh, 160014, India.
Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Biochem Genet. 2019 Feb;57(1):129-146. doi: 10.1007/s10528-018-9880-7. Epub 2018 Aug 2.
CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (p < 0.001, OR 3.121, 95% CI 1.926-5.056 and p < 0.001, OR 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with p < 0.001, OR 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (p < 0.001, OR 3.693, 95% CI 2.031-6.716; p < 0.001, OR 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (p = 0.010, OR 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (p < 0.001, OR 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (p = 0.039, OR 5.052, 95% CI 1.081-23.602; and p = 0.025, OR 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (p < 0.000, OR 2.964, 95% CI 1.747-5.027; and p < 0.000, OR 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (p < 0.001, OR 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent.
冠心病(CAD)的发病率在全球范围内正呈地方病态势。最近,促炎和抗炎细胞因子在动脉粥样硬化斑块形成中的作用已得到探索,但它们的基因多态性与冠心病的关联尚未确立。本研究旨在调查北印度人群中白细胞介素-8(IL-8)-251A/T(rs4073)和白细胞介素-10(IL-10)-592C/A(rs1800872)多态性与冠心病风险的关联。通过扩增阻滞突变系统聚合酶链反应(ARMS-PCR)对1000名受试者(500名经血管造影证实的冠心病患者和500名对照)进行基因分型。结果显示这两种多态性均与冠心病存在显著的风险关联。在校正混杂因素后,发现IL-8 rs4073的杂合子和突变基因型均与疾病风险相关(分别为p < 0.001,比值比[OR] 3.121,95%置信区间[CI] 1.926 - 5.056和p < 0.001,OR 3.116,95% CI 1.952 - 4.973),但只有IL-10 rs1800872的突变AA基因型与疾病风险相关,p < 0.001,OR 4.106,95% CI 2.160 - 7.806)。根据性别对样本进行分层分析显示,男性中IL-8 rs4073的杂合子和突变型与冠心病相关(分别为p < 0.001,OR 3.693,95% CI 2.031 - 6.716;p < 0.001,OR 3.288,95% CI 1.848 - 5.851),而在女性中只有突变型与疾病风险相关(p = 0.010,OR 2.867,95% CI 1.284 - 6.404);对于IL-10 rs1800872,只有突变基因型AA在男性中与冠心病风险相关(p < 0.001,OR 5.821,95% CI 2.831 - 11.970)。基于年龄的分层分析显示,与40岁以上受试者中疾病风险的杂合子和突变基因型关联相比(分别为p < 0.000,OR 2.964,95% CI 1.747 - 5.027;和p < 0.000,OR 2.859,95% CI 1.716 - 4.762),40岁以下受试者中IL-8 rs4073的杂合子和突变基因型的风险显著更高(分别为p = 0.039,OR 5.052,95% CI 1.081 - 23.602;和p = 0.025,OR 5.533,95% CI 1.239 - 24.704)。对于IL-10 rs1800872,风险关联仅在40岁以上的受试者中出现(p < 0.001,OR 5.049,95% CI 2.414 - 10.561)。本研究表明,在北印度人群中,IL-8-251A/T(rs4073)和IL-10 -592C/A(rs1800872)与冠心病存在关联,且这种关联具有性别和年龄依赖性。