Genetic variants in CHI3L1 influencing YKL-40 levels: resequencing 900 individuals and genotyping 9000 individuals from the general population.
BACKGROUND
Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.


METHODS
We resequenced the promoter, all 10 exons and exon-flanking intron segments of CHI3L1 in 904 individuals from the Danish general population (n=8899) with extreme plasma YKL-40 levels, adjusted for age. To potentially identify clinically important genetic variants with elevated plasma YKL-40 levels, we included twice as many individuals with the highest plasma YKL-40 levels (n=603) compared with the lowest plasma YKL-40 levels (n=301). Next, we mapped linkage disequilibrium for all variants with a minor allele frequency (MAF)>0.005. Finally, all participants were genotyped for eight variants that had divergent MAFs in the two extreme plasma YKL-40 groups.


RESULTS
We identified 59 genetic variants in CHI3L1. Fifteen of the genetic variants were associated with plasma YKL-40 levels. Three promoter SNPs, 1 non-synonymous SNP, and four intronic SNPs in CHI3L1 were associated with plasma YKL-40 levels at or below genome-wide association significance levels (unadjusted p for trend: from 4 × 10(-8) to 6 × 10(-243); age adjusted percentiles p for trend: from 3 × 10(-12) to 2 × 10(-304)).


CONCLUSIONS
In a systematic search to identify genetic variants influencing plasma YKL-40 levels, we identified eight SNPs associated with plasma YKL-40 levels in the general population.
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Herlev, Denmark.
Alisa D
AD
Kjaergaard
Julia S
JS
Johansen
Børge G
BG
Nordestgaard
Stig E
SE
Bojesen
D054392:Adipokines / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D004252:DNA Mutational Analysis; D003718:Denmark; D006801:Humans; D037102:Lectins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium / Q000235:genetics; D011446:Prospective Studies; D044465:White People / Q000235:genetics
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins
Genetic epidemiology; Linkage; Oncology; Screening