Article Text

PDF
Original article
Genetic variants in CHI3L1 influencing YKL-40 levels: resequencing 900 individuals and genotyping 9000 individuals from the general population
  1. Alisa D Kjaergaard1,2,
  2. Julia S Johansen2,3,
  3. Børge G Nordestgaard1,2,4,
  4. Stig E Bojesen1,2,4
  1. 1Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Herlev, Denmark
  2. 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Herlev, Denmark
  3. 3Department of Medicine and Oncology, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Herlev, Denmark
  4. 4The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Herlev, Denmark
  1. Correspondence to Dr Stig E Bojesen, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Copenhagen, Herlev DK-2730, Denmark; Stig.Egil.Bojesen{at}regionh.dk

Abstract

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.

  • Genetic epidemiology
  • Linkage
  • Oncology
  • Screening

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.