The Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.
School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
Int J Mol Sci. 2019 Mar 7;20(5):1174. doi: 10.3390/ijms20051174.
Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the gene promoter region polymorphism rs3735167 ( = 2.35 × 10). In the CAD population, borderline significance was noted between polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan⁻Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels.
趋化素是一种新型脂肪因子，与代谢、炎症和动脉粥样硬化性疾病有关。我们旨在通过全基因组关联研究（GWAS）确定趋化素水平的遗传基础，并研究多态性和循环趋化素水平在冠状动脉疾病（CAD）长期预后中的作用。共招募了 2197 名来自台湾生物银行（TWB）的参与者进行 GWAS 分析，招募了 481 名经血管造影证实的 CAD 患者进行长期预后分析。在趋化素水平的 GWAS 中发现了一个具有单一独立关联信号的全基因组显著位点，其峰值关联位于基因启动子区域多态性 rs3735167（ = 2.35 × 10）。在 CAD 人群中，rs3735167 多态性与趋化素水平之间存在边缘显著相关性，而高趋化素水平与肥胖、女性、糖尿病、高血压、当前吸烟、高血小板和白细胞计数、贫血、肾功能受损、高 C 反应蛋白（CRP）水平和多血管疾病有关。Kaplan⁻Meier 生存曲线表明，高趋化素和 CRP 水平的患者，而不是 rs3735167 多态性的患者，生存率较低，合并脑心血管事件发生率较高。联合趋化素和 CRP 水平进一步表明，从低风险亚组到高风险亚组，不良临床结局呈逐步增加趋势。总之，rs3735167 是台湾人趋化素水平的主要多态性。趋化素水平而非 rs3735167 基因型预测 CAD 的长期预后，尤其是与 CRP 水平联合时。
