Mastana Sarabjit, Prakash Swayam, Akam Elizabeth C, Kirby Melissa, Lindley Martin R, Sinha Nakul, Agrawal Suraksha
Human Genomics Lab, School of Sport, Exercise and Heath Sciences, Loughborough University, Loughborough, Leicestershire LE11 3TU, United Kingdom.
Department of Hematology, SGPGIMS, Lucknow, India.
Gene. 2017 Sep 10;628:301-307. doi: 10.1016/j.gene.2017.07.050. Epub 2017 Jul 21.
Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α -308 (G/A), TNF-β +252 (A/G), IL-6 -174 (G/C) and IL-6 -597 (G/A), and IFN-ɣ +874 (T/A) with coronary artery disease (CAD) among north Indian patients.
143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α -308 (G/A) (rs1800797), TNF-β +252 (A/G) (rs909253), IL-6 -174 (G/C) (rs1800795), IL6 -597 (G/A) (rs1800797), and IFN-ɣ +874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p≤0.05 was considered significant.
Significant risk association with CAD was found for TNF-α -308 (G/A) "A" allele (OR=5.6, CI 1.8-17.4, p=0.001) and TNF-β +252 (A/G) "G" allele (OR=3.4, CI=1.9-6.0, p<0.001). However, no statistical significance was found for IL-6 -174 (G/C) or IL6 -597 (G/A), with CAD. TNF-α -308 (G/A), and TNF-β +252 (A/G) haplotype "GG" "AG" increased CAD risk significantly (GG haplotype, adjusted OR=2.6, CI 1.4-5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2-33.35, p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet.
The present study found significant risk association for TNF-α -308 (G/A), and TNF-β +252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population.
细胞因子调节炎症分子的表达，这些炎症分子会破坏动脉粥样硬化斑块的稳定性。本研究聚焦于研究炎症细胞因子多态性，如肿瘤坏死因子-α（TNF-α）-308（G/A）、肿瘤坏死因子-β（TNF-β）+252（A/G）、白细胞介素-6（IL-6）-174（G/C）和IL-6 -597（G/A）以及干扰素-γ（IFN-γ）+874（T/A）与印度北部患者冠状动脉疾病（CAD）之间的关联。
本研究招募了143例CAD患者和137例正常健康对照。采用高盐析法进行DNA提取。通过TaqMan®SNP基因分型检测对TNF-α -308（G/A）（rs1800797）、TNF-β +252（A/G）（rs909253）、IL-6 -174（G/C）（rs1800795）、IL-6 -597（G/A）（rs1800797）和IFN-γ +874（T/A）（rs2430561）单核苷酸多态性（SNP）进行基因分型。使用SPSS v 22.0和SNPStats进行不同的统计分析。p≤0.05被认为具有统计学意义。
发现TNF-α -308（G/A）“A”等位基因（比值比[OR]=5.6，置信区间[CI] 1.8 - 17.4，p = 0.001）和TNF-β +252（A/G）“G”等位基因（OR = 3.4，CI = 1.9 - 6.0，p < 0.001）与CAD存在显著风险关联。然而，未发现IL-6 -174（G/C）或IL-6 -597（G/A）与CAD有统计学意义。在对年龄、性别、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、载脂蛋白B（APOB）、吸烟和饮食进行调整后，TNF-α -308（G/A）和TNF-β +252（A/G）单倍型“GG”“AG”显著增加了CAD风险（GG单倍型，调整后OR = 2.6，CI 1.4 - 5.0，p = 0.003；AG单倍型OR = 8.5，CI 2.2 - 33.35，p = 0.002）。
本研究发现TNF-α -308（G/A）和TNF-β +252（A/G）的基因型、等位基因和单倍型与印度北部人群的CAD存在显著风险关联。
