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Int. J. Mol. Sci. 2014, 15(12), 22421-22437; doi:10.3390/ijms151222421

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

1
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan
2
Department of Life Science, Chinese Culture University, Taipei 11114, Taiwan
3
The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
4
The Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan
5
Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taipei 33305, Taiwan
6
School of Medicine, Tzu Chi University, Hualien 97071, Taiwan
*
Author to whom correspondence should be addressed.
Received: 29 September 2014 / Revised: 19 November 2014 / Accepted: 24 November 2014 / Published: 4 December 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: circulating YKL-40 level; CHI3L1 gene variants; peripheral artery disease; association study; haplotype; risk factor circulating YKL-40 level; CHI3L1 gene variants; peripheral artery disease; association study; haplotype; risk factor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wu, S.; Hsu, L.-A.; Cheng, S.-T.; Teng, M.-S.; Yeh, C.-H.; Sun, Y.-C.; Huang, H.-L.; Ko, Y.-L. Circulating YKL-40 Level, but not CHI3L1 Gene Variants, Is Associated with Atherosclerosis-Related Quantitative Traits and the Risk of Peripheral Artery Disease. Int. J. Mol. Sci. 2014, 15, 22421-22437.

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