Plasma levels of the proinflammatory chitin-binding glycoprotein YKL-40,variation in the chitinase 3-like 1 gene (CHI3l1),and incident cardiovascular events

Background-ykl-40,encoded by the chitinase 3-like 1 (chi3l1) gene,is a chitinase-like protein involved in innate immune function hypothesized to play a role in the progression of atherosclerosis that may have differential roles in myocardial infarction (mi),as compared to stroke. methods and results-in a nested case-control study conducted within a prospective cohort of 23 294 initially healthy women of european ancestry,we (1) measured plasma concentration of ykl-40 among 359 participants who subsequently developed cardiovascular events and among 359 age-,smoking-,and hormone replacement therapy-matched participants who remained free of disease during 17 years of follow-up,(2) compared effects of ykl-40 on vascular risk to that associated with 3 alternative inflammatory biomarkers (high-sensitivity c-reactive protein) ([hscrp],soluble intracellular adhesion molecule 1,and fibrinogen),and (3) evaluated the role of 41 single-nucleotide polymorphisms (snps) in the chitinase 3-like 1 gene (chi3l1) as determinants of ykl-40 levels and incident vascular events. ykl-40 levels were higher in women with hypertension,diabetes,and obesity and correlated modestly with high-density lipoprotein cholesterol,triglycerides,and hscrp,but not with low-density lipoprotein cholesterol. baseline ykl-40 level was significantly associated with incident thromboembolic stroke with a magnitude of effect (a 40% per quartile increase in odds ratio [or],p=0.019) comparable to that of hscrp (a 52% per quartile increase in or,p=0.006). by contrast,no significant association was observed between ykl-40 and incident mi. genetic variation in chi3l1 was strongly associated with ykl-40 levels; however,in this sample set,we did not observe a statistically significant association between genotype and future vascular events. conclusions-among initially healthy u.s. women,plasma levels of the proinflammatory chitenase-like protein,ykl-40,were influenced by environmental as well as genetic factors and predicted incident thromboembolic stroke,but not mi,a differential effect consistent with limited previous data. © 2014 the authors.