Department of Biochemistry, KGMU, Lucknow 226003, India; Department of Zoology, University of Lucknow, Lucknow 226007, India.
Department of Clinical Immunology, SGPGIMS, Lucknow 226014, India.
Cytokine. 2018 Oct;110:131-136. doi: 10.1016/j.cyto.2018.04.035. Epub 2018 May 4.
Tumor necrosis factor-alpha (TNF-α) are considered as a pro inflammatory and interleukin-10 (IL-10) anti inflammatory have been shown to predict the risk of incident of coronary artery disease (CAD). The polymorphism at promoter of TNF-α and IL-10 has been shown to increase transcriptional activity of the gene and play a important role in patho physiology of CAD. Aim of present study is to examine the impact of the TNF-α and IL-10 variant allele on various markers of the CAD and to study its relation with circulating TNF-α and IL-10 levels.
The -308 G/A & -238 G/A of TNF-α and -1082 G/A & -819 C/T of IL-10 gene polymorphism has been studied in 301 diagnosed CAD subjects (Age 51.50 ± 9.28; BMI 25.30 ± 3.58) and 305 healthy controls (Age 51.57 ± 9.50; BMI 24.06 ± 7.26). These polymorphism of TNF-α and IL-10 were detected by real time PCR by using Taqman SNP genotyping assay. Furthermore serum TNF-alpha and IL-10 levels were also measured by ELISA.
Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p > 0.05). On allele contrast, significant association with susceptibility to CAD was detected with polymorphisms in TNF-α -308 G/A, that variant genotype GA + AA (dominant model) (p = 0.030: OR = 1.61: 95% CI = 1.06-2.44) and variant allele (A) (p = 0.006: OR = 1.71: 95% CI = 1.17-2.51) of TNF-α 308 G/A gene was significant highly observed in the cases as compared to control group. Furthermore, variant genotype CT + TT (dominant model) (p = 0.004: OR = 1.62: 95% CI = 1.17-2.24) and variant allele (T) (p < 0.001: OR = 1.49: 95% CI = 1.17-1.89) of IL-10 -819 C/T gene was significant highly observed in the cases as compared to control group.
Our results suggest that the TNF-α G-308A polymorphism independently associated with DBP, cholesterol, triglyceride, LDL, TNF-α and IL-10 levels which may be leads to the development of coronary artery disease of North Indians.
肿瘤坏死因子-α（TNF-α）被认为是一种促炎细胞因子，而白细胞介素-10（IL-10）则具有抗炎作用，已被证明可预测冠心病（CAD）的发病风险。TNF-α 和 IL-10 启动子的多态性已被证明可增加基因的转录活性，并在 CAD 的病理生理学中发挥重要作用。本研究旨在探讨 TNF-α 和 IL-10 变异等位基因对 CAD 各种标志物的影响，并研究其与循环 TNF-α 和 IL-10 水平的关系。
研究了 301 例确诊 CAD 患者（年龄 51.50±9.28；BMI 25.30±3.58）和 305 名健康对照者（年龄 51.57±9.50；BMI 24.06±7.26）中 TNF-α 的-308 G/A 和-238 G/A 以及 IL-10 的-1082 G/A 和-819 C/T 基因多态性。通过 Taqman SNP 基因分型检测，使用实时 PCR 检测 TNF-α 和 IL-10 的这些多态性。此外，还通过 ELISA 测量了血清 TNF-α 和 IL-10 水平。
对照组的等位基因和基因型频率未偏离 Hardy-Weinberg 平衡（p＞0.05）。在等位基因对比中，TNF-α-308 G/A 多态性与 CAD 易感性显著相关，变异基因型 GA+AA（显性模型）（p=0.030：OR=1.61：95%CI=1.06-2.44）和变异等位基因（A）（p=0.006：OR=1.71：95%CI=1.17-2.51）在病例组中明显高于对照组。此外，与对照组相比，IL-10-819 C/T 基因的变异基因型 CT+TT（显性模型）（p=0.004：OR=1.62：95%CI=1.17-2.24）和变异等位基因（T）（p＜0.001：OR=1.49：95%CI=1.17-1.89）在病例组中也明显升高。
我们的结果表明，TNF-α G-308A 多态性与 DBP、胆固醇、甘油三酯、LDL、TNF-α 和 IL-10 水平独立相关，这可能导致北印度人冠心病的发生。
