Journalartikel

Jahr der Veröffentlichung: 2014

Seiten: e1004854-

Zeitschrift: PLoS Genetics

Bandnummer: 10

Heftnummer: 12

ISSN: 1553-7390

DOI Link: https://doi.org/10.1371/journal.pgen.1004854

Verlag: Public Library of Science

Abstract: 
Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p<5.0x10(-8)) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8x10(-14), beta = -0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r(2) = 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p<0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations.

Harvard-Zitierstil: Tönjes, A., Scholz, M., Breitfeld, J., Marzi, C., Grallert, H., Gross, A., et al. (2014) Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin, PLoS Genetics, 10(12), p. e1004854. https://doi.org/10.1371/journal.pgen.1004854

APA-Zitierstil: Tönjes, A., Scholz, M., Breitfeld, J., Marzi, C., Grallert, H., Gross, A., Ladenvall, C., Schleinitz, D., Krause, K., Kirsten, H., Laurila, E., Kriebel, J., Thorand, B., Rathmann, W., Groop, L., Prokopenko, I., Isomaa, B., Beutner, F., Kratzsch, J., ...Kovacs, P. (2014). Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin. PLoS Genetics. 10(12), e1004854. https://doi.org/10.1371/journal.pgen.1004854