Variation in CHI3LI in relation to type 2 diabetes and related quantitative traits.
BACKGROUND
CHI3LI encoding the inflammatory glycoprotein YKL-40 is located on chromosome 1q32.1. YKL-40 is involved in inflammatory processes and patients with Type 2 Diabetes (T2D) have elevated circulating YKL-40 levels which correlate with their level of insulin resistance. Interestingly, it has been reported that rs10399931 (-329 G/A) of CHI3LI contributes to the inter-individual plasma YKL-40 levels in patients with sarcoidosis, and that rs4950928 (-131 C/G) is a susceptibility polymorphism for asthma and a decline in lung function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes thereof the CHI3LI locus might influence risk of T2D. The aim of the present study was to investigate the putative association between SNPs and haplotype blocks of CHI3LI and T2D and T2D related quantitative traits.


RESULTS
Eleven SNPs of CHI3LI were genotyped in 6514 individuals from the Inter99 cohort and 2924 individuals from the outpatient clinic at Steno Diabetes Center. In cas-control studies a total of 2345 T2D patients and 5302 individuals with a normal glucose tolerance test were examined. We found no association between rs10399931 (OR, 0.98 (CI, 0.88-1.10), p = 0.76), rs4950928 (0.98 (0.87-1.10), p = 0.68) or any of the other SNPs with T2D. Similarly, we found no significant association between any of the 11 tgSNPs and T2D related quantitative traits, all p>0.14. None of the identified haplotype blocks of CHI3LI showed any association with T2D, all p>0.16.


CONCLUSIONS
None of the examined SNPs or haplotype blocks of CHI3LI showed any association with T2D or T2D related quantitative traits. Estimates of insulin resistance and dysregulated glucose homeostasis in T2D do not seem to be accounted for by the examined variations of CHI3LI.
Rathcke
Camilla Noelle
CN
Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. cnr@dadlnet.dk
Holmkvist
Johan
J
Jørgensen
Torben
T
Borch-Johnsen
Knut
K
Hansen
Torben
T
Pedersen
Oluf Borbye
OB
Vestergaard
Henrik
H
D054392:Adipokines; D000328:Adult; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance; D037102:Lectins; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins