Zhang Hongsong, Nie Shaofang, Chen Qianwen, Wang Pengyun, Xu Chengqi, Tu Xin, Zhang Lifang, Kenneth Wang Qing, Zha Lingfeng
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cytokine. 2023 Apr;164:156142. doi: 10.1016/j.cyto.2023.156142. Epub 2023 Feb 18.
Studies have confirmed that the IL-23R/IL-17A axis plays an important role in the development of autoimmune and inflammatory diseases. However, its role in coronary artery disease (CAD) remains unclear. Here, we conducted a large sample case-control study to investigate the association between the IL23R/IL17A axis and CAD in the Chinese Han population.
Two SNPs, rs2275913: G>A (IL17A) and rs6682925: T>C (IL23R), were genotyped in 3042 CAD cases and 3216 controls using the high-resolution melt technology (HRM). Logistic regression analyses were used to adjust the traditional risk factors for CAD and perform the gene interaction analyses. Multiple linear regression analyses were used to study the relationships between the selected SNPs and the levels of serum lipids. In addition, meta-analysis also was performed for the association between rs6682925 and rs2275913 with CAD in different popolations.
Our case-control and meta-analysis for single SNPs demonstrated that the frequencies of the alleles and the distribution of the genotypes had no significant differences in CAD cases compared with controls. In the stratified analysis, we observed that the frequency of the IL17A rs2275913-A allele was more epidemic in early-onset CAD than in the controls (P = 0.005, OR = 1.209, 95% CI: 1.059-1.382), and the minor allele C of rs6682925 was associated with a decreased level of serum total cholesterol under a recessive model (P = 0.011). We demonstrated a significant interaction between rs6682925 and rs2275913 and CAD in the Chinese Han population. Four genotypes (CTGG, CCAA, CCAG, CCGG) were significantly associated with CAD (P = 2.94 × 10, OR = 0.619, 95% CI: 0.478-0.803; P = 0.01, OR = 1.808, 95% CI: 1.152-1.869; P = 6 × 10, OR = 2.179, 95% CI: 1.558-3.049; P = 0.001, OR = 1.883, 95% CI: 1.282-2.762, respectively).
Our study found no single SNP of rs2275913 in IL17A and rs6682925 in IL23R was associated with CAD in the Chinese population, but the interaction of them were significantly associated with CAD susceptibility, highlighting the key role of the IL-23R/IL-17A axis in the development of CAD. In addition, we also found rs2275913 was associated with early-onset CAD and rs6682925 was associated with total cholesterol levels, which will contribute to the clinical stratified management of this common disease.
研究已证实白细胞介素-23受体/白细胞介素-17A（IL-23R/IL-17A）轴在自身免疫性疾病和炎症性疾病的发展中起重要作用。然而，其在冠状动脉疾病（CAD）中的作用仍不清楚。在此，我们进行了一项大样本病例对照研究，以调查中国汉族人群中IL23R/IL17A轴与CAD之间的关联。
采用高分辨率熔解技术（HRM）对3042例CAD患者和3216例对照进行两个单核苷酸多态性（SNP），即rs2275913：G>A（IL17A）和rs6682925：T>C（IL23R）的基因分型。采用逻辑回归分析调整CAD的传统危险因素并进行基因相互作用分析。采用多元线性回归分析研究所选SNP与血脂水平之间的关系。此外，还对rs6682925和rs2275913与不同人群CAD之间的关联进行了荟萃分析。
我们对单个SNP的病例对照研究和荟萃分析表明，与对照组相比，CAD患者的等位基因频率和基因型分布无显著差异。在分层分析中，我们观察到IL17A rs2275913-A等位基因在早发性CAD中的流行程度高于对照组（P = 0.005，比值比[OR]=1.209，95%置信区间[CI]：1.059-1.382），并且在隐性模型下，rs6682925的次要等位基因C与血清总胆固醇水平降低相关（P = 0.011）。我们证实在中国汉族人群中rs6682925与rs2275913以及CAD之间存在显著的相互作用。四种基因型（CTGG、CCAA、CCAG、CCGG）与CAD显著相关（P = 2.94×10，OR = 0.619，95%CI：0.478-0.803；P = 0.01，OR = 1.808，95%CI：1.152-1.869；P = 6×10，OR = 2.179，95%CI：1.558-3.049；P = 0.001，OR = 1.883，95%CI：1.282-2.762）。
我们的研究发现，在中国人群中IL17A中的rs2275913和IL23R中的rs6682925这两个单个SNP与CAD无关，但它们的相互作用与CAD易感性显著相关，突出了IL-23R/IL-17A轴在CAD发展中的关键作用。此外，我们还发现rs2275913与早发性CAD相关，rs6682925与总胆固醇水平相关，这将有助于对这种常见疾病进行临床分层管理。
