Circulating YKL-40 Level, but not CHI3L1 Gene Variants, Is Associated with Atherosclerosis-Related Quantitative Traits and the Risk of Peripheral Artery Disease

International Journal of Molecular Sciences

Semon Wu⁴  Lung-An Hsu¹  Shih-Tsung Cheng³  Ming-Sheng Teng⁴  Ching-Hua Yeh⁴  Yu-Chen Sun²  Hsuan-Li Huang⁴  Yu-Lin Ko⁴ 

[1] The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan; E-Mail:;Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taipei 33305, Taiwan; E-Mail:;The Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan; E-Mail:;Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan; E-Mails:

关键词: circulating YKL-40 level;    CHI3L1 gene variants;    peripheral artery disease;    association study;    haplotype;    risk factor;   

DOI  :  10.3390/ijms151222421

来源: mdpi

【 摘 要 】

YKL-40, a pleotropic cytokine, is emerging as a risk factor and a prognostic predictor of atherosclerotic cardiovascular disease. We attempted to elucidate the genetic, clinical and biochemical correlates of circulating YKL-40 level and, by combining it with CHI3L1 gene variants, with the risk and long-term mortality of peripheral artery disease (PAD). Plasma YKL-40 concentrations were measured in 612 Taiwanese individuals who had no clinically overt systemic disease. Clinical parameters, CHI3L1 gene promoter variants and 18 biomarker levels were analyzed. Eighty-six PAD patients were further enrolled for analysis. Significant associations were found between CHI3L1 genotypes/haplotypes and YKL-40 levels for the health examination subjects (smallest p = 8.36 × 10⁻⁷ for rs4950928 and smallest p = 1.72 × 10⁻¹⁰ for haplotype TGG) and also for PAD patients. For the health examination subjects, circulating YKL-40 level, but not CHI3L1 gene variants, were positively associated with age, smoking, and circulating levels of triglyceride, lipocalin 2 and multiple inflammatory biomarkers and negatively associated with low-density-lipoprotein cholesterol levels. Circulating YKL-40 level is also significantly associated with the risk of PAD (p = 3.3 × 10⁻²³). Circulating YKL40 level, but not CHI3L1 gene promoter variants, is associated with the risk of PAD in Taiwanese. The association of YKL-40 levels with multiple quantitative traits relating to the risk of PAD may provide a molecular basis linking YKL-40 to atherosclerotic cardiovascular disease.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.