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Tönjes, A.* ; Scholz, M.* ; Breitfeld, J.* ; Marzi, C. ; Grallert, H. ; Gross, A.* ; Ladenvall, C.* ; Schleinitz, D.* ; Krause, K.P.* ; Kirsten, H.* ; Laurila, E.* ; Kriebel, J. ; Thorand, B. ; Rathmann, W.* ; Groop, L.C.* ; Prokopenko, I.* ; Isomaa, B.* ; Beutner, F.* ; Kratzsch, J.K.* ; Thiery, J.J.* ; Faßhauer, M.* ; Klöting, N.* ; Gieger, C. ; Blüher, M.* ; Stumvoll, M.W.* ; Kovacs, P.*

Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating serum chemerin.

PLoS Genet. 10:e1004854 (2015)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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<5.0×10−8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8×10−14, beta = −0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2= 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Zeitschrift PLoS Genetics
Quellenangaben Band: 10, Heft: 12, Seiten: , Artikelnummer: e1004854 Supplement: ,
Verlag Public Library of Science (PLoS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
CCG Nutrigenomics and Type 2 Diabetes (KKG-KDN)
POF Topic(s) 30202 - Environmental Health
90000 - German Center for Diabetes Research
30502 - Diabetes: Pathophysiology, Prevention and Therapy
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-002
G-501900-402
G-504091-004
G-504000-002
G-521600-002
PubMed ID 25521368
DOI 10.1371/journal.pgen.1004854
WOS ID WOS:000346649900053
Scopus ID 84919594987
Erfassungsdatum 2015-01-01
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