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.
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.
Authors: Amal Ahmed Abd El-Fattah; Nermin Abdel Hamid Sadik; Olfat Gamil Shaker; Amal Mohamed Kamal Journal: Mediators Inflamm Date: 2018-10-25 Impact factor: 4.711
Authors: Stine B Thomsen; Anette P Gjesing; Camilla N Rathcke; Claus T Ekstrøm; Hans Eiberg; Torben Hansen; Oluf Pedersen; Henrik Vestergaard Journal: PLoS One Date: 2015-07-21 Impact factor: 3.240
Authors: Sarah E Bergen; Mikael Landén; Ruyue Zhang; Jie Song; Anniella Isgren; Joel Jakobsson; Kaj Blennow; Carl M Sellgren; Henrik Zetterberg Journal: Transl Psychiatry Date: 2020-02-05 Impact factor: 6.222