Interleukin‐6 (IL‐6), a pivotal pro‐inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL‐6 levels are largely determined by the genetic variant in IL‐6, this study was conducted to investigate whether the IL‐6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL‐6 gene) C allele was linked to higher levels of low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high‐density lipoprotein cholesterol (HDL‐C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL‐6 inhibition with ziltivekimab or canakinumab may benefit high‐risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.

中文翻译：

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促炎细胞因子变体对心脏代谢特征和早发冠状动脉疾病的影响：系统评价和荟萃分析

白细胞介素-6 (IL-6) 是一种关键的促炎细胞因子，与血管壁增厚和动脉粥样硬化病变密切相关。由于血清 IL-6 水平很大程度上由遗传变异决定白介素-6，本研究旨在调查是否白介素-6变异会影响心脏代谢特征和早发冠状动脉疾病（PCAD）的风险。 PubMed、Cochrane 图书馆、Central、护理和联合健康文献累积索引 (CINAHL) 以及临床试验网检索时间为2022年5月13日至2023年6月28日。总共纳入了40项研究（26,543人）进行分析。 rs1800795（函数变体白介素-6基因）C 等位基因与较高水平的低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、空腹血糖（FPG）、体重指数（BMI）和腰围（WC）有关，并且降低高密度脂蛋白胆固醇（HDL-C）水平。然而，未观察到 rs1800795 与甘油三酯 (TG)、收缩压 (SBP) 和舒张压 (DBP) 之间存在显着关联。有趣的是，在 rs1800795 和 PCAD 之间检测到显着关联。亚组分析表明，rs1800795 对心脏代谢危险因素的影响在白种人中显着，但在肥胖患者中更强。相比之下，rs1800795 对 PCAD 的影响在棕色人种人群中显着。总之，rs1800795 对心脏代谢危险因素和 PCAD 有轻微但显着的影响。使用 ziltivekimab 或 canakinumab 抑制 IL-6 可能有益于具有 rs1800795 的高危人群（例如棕色人种人群、白种人、肥胖患者等）预防 PCAD。