title: Circulating YKL-40 level, but not CHI3L1 gene variants, is associated with atherosclerosis-related quantitative traits and the risk of peripheral artery disease.
abstract: 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.
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan. semonwu@yahoo.com.tw.
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.affiliation: The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan. hsula@adm.cgmh.org.tw.
authors.forename: Lung-An
authors.initials: LA
authors.lastname: Hsu
authors.affiliation: The Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan. chengshihtsung@gmail.com.
authors.forename: Shih-Tsung
authors.initials: ST
authors.lastname: Cheng
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan. vincent@tzuchi.com.tw.
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Teng
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan. aethiopica@gmail.com.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taipei 33305, Taiwan. sun036@adm.cgmh.org.tw.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Sun
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan. huang304@ms11.hinet.ne.
authors.forename: Hsuan-Li
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan. yulinkotco@tzuchi.com.tw.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Ko
mesh_terms: D054392:Adipokines / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000235:genetics* / Q000401:mortality; D010808:Physical Examination; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D012307:Risk Factors
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins