Department of Chemical Pathology, Army Medical College, National University of Science and Technology (NUST), Islamabad, Pakistan.
Cardiovascular Genetics Department, Cardiovascular Genetics Institute, University College London, London, UK.
Postgrad Med J. 2017 Apr;93(1098):209-214. doi: 10.1136/postgradmedj-2016-134167. Epub 2016 Aug 24.
Genetic information has the potential to create a more personalised, prompt, early and accurate risk evaluation. The effect of these genetic variants on the serum biomarker levels (phenotype) needs to be studied to assess their potential causal role in the pathogenesis of premature coronary artery disease (PCAD). Objectives were to determine the genotypic distribution of interleukin (, tumour necrosis factor- () and single nucleotide polymorphisms (SNPs) in Pakistani PCAD cases and disease free controls and to study the effect of these gene polymorphisms on the serum cytokine levels (IL18, TNFA, IL6 and IL10) and cytokine imbalance (IL18:IL10 and TNFA:IL10).
The case-control study was carried out in National University of Sciences and Technology, Islamabad in collaboration with the Cardiovascular Genetics Institute, University College London, UK. Subjects (n=340) with >70% stenosis in at least a single major coronary artery on angiography were taken as PCAD cases along with 310 angiographically verified controls. ELISA was performed for measuring the concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using TAQMAN assay.
The risk allele frequencies (RAFs) of rs1800795 and rs187238 cytokine gene promoter SNPs were significantly higher in the PCAD cases as compared with the controls. Serum IL18 and IL10 levels were significantly greater in the IL18 rs187238 GG genotype patients while serum IL18 and IL6 levels were significantly higher in patients having the rs1800795 CC genotype. rs1946519 significantly altered the IL18, TNFA, IL6, IL18/IL10 and TNFA/IL10 ratio levels followed by SNP rs1800629 which significantly altered the serum levels of IL18, IL18:IL-0 and TNFA:IL10 ratios.
The association of the selected SNPs with differential serum cytokine levels especially the cytokine imbalance points towards their potential causal role in the immune inflammatory pathogenic pathway of PCAD.
遗传信息有可能实现更个性化、更及时、更早和更准确的风险评估。需要研究这些遗传变异对血清生物标志物水平（表型）的影响，以评估它们在早发性冠心病（PCAD）发病机制中的潜在因果作用。目的是确定巴基斯坦 PCAD 病例和无疾病对照中白细胞介素（IL）、肿瘤坏死因子（TNF）-和单核苷酸多态性（SNP）的基因型分布，并研究这些基因多态性对血清细胞因子水平（IL18、TNFA、IL6 和 IL10）和细胞因子失衡（IL18:IL10 和 TNFA:IL10）的影响。
这项病例对照研究是在巴基斯坦伊斯兰堡的国立科技大学与英国伦敦大学学院心血管遗传学研究所合作进行的。在血管造影中至少一条主要冠状动脉有 >70%狭窄的患者被视为 PCAD 病例，同时还纳入了 310 名经血管造影证实的对照。采用 ELISA 法测定血清 IL18、TNFA、IL6 和 IL10 浓度。采用 TAQMAN 法进行基因分型。
与对照组相比，PCAD 病例中 rs1800795 和 rs187238 细胞因子基因启动子 SNP 的风险等位基因频率（RAF）明显更高。IL18 rs187238 GG 基因型患者的血清 IL18 和 IL10 水平显著升高，而 rs1800795 CC 基因型患者的血清 IL18 和 IL6 水平显著升高。rs1946519 显著改变了 IL18、TNFA、IL6、IL18/IL10 和 TNFA/IL10 比值水平，其次是 rs1800629，它显著改变了血清中 IL18、IL18:IL-0 和 TNFA:IL10 比值水平。
所选 SNP 与血清细胞因子水平的差异相关，特别是细胞因子失衡，这表明它们在 PCAD 的免疫炎症发病机制中可能具有潜在的因果作用。
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