Variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and prediction of fatal and non-fatal ischemic stroke

Abstract

Background: Polymorphisms of CHI3L1 are associated with inter-individual YKL-40 levels and YKL-40 is associated with an increased mortality and is elevated in patients with cardiovascular disease. We investigated the association between single nucleotide polymorphisms (SNPs) of CHI3L1, serum YKL-40 levels and all-cause and cardiovascular mortality and first-time incidence of myocardial infarction, ischemic heart disease (IHD) and stroke. Methodology/Principal Findings: 12 SNPs of CHI3L1 were genotyped and serum YKL-40 was measured in 2656 Danes representative of the general population. Median follow-up period was 15 (0-16) years. Admission data and deaths were ascertained from registers from the Danish National Board of Health. Fourth quartile YKL-40 levels were associated with an increased mortality risk of ischemic stroke (HR 2.44 (1.01-5.88), p = 0.041) and so were homozygotes of the minor allele of rs872129 (HR 9.35 (1.25-69.87, p = 0.022)). Both continuous YKL-40 levels and 4th quartile YKL-40 values (>85 ng/ml) were associated with all-cause mortality (HRs 1.22 (95% CI, 1.10-1.35), p<0.0001, and 1.40 (1.15-1.71), p<0.0001), an increased risk of first-time stroke (HR 1.16 (1.01-1.33), p = 0.04, and 1.63 (1.23-2.16), p = 0.001) and a decreased risk of incidence of IHD (HR 0.77 (0.65-0.91), p = 0.002, and 0.61 (0.44-0.85), p = 0.003). Conclusions/Signficance: High YKL-40 levels (>85 ng/ml) and rs872129 were associated with an increased mortality risk of ischemic stroke, but high YKL-40 levels were also inverse related with the risk of incidence of IHD. This could be a chance finding but could also elucidate that YKL-40 plays different roles in development of thromboembolisms versus the formation of local thrombosis. © 2012 Rathcke et al.