Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating serum chemerin
| Autor: | Esa Laurila, Jana Breitfeld, Peter Kovacs, Nora Klöting, Barbara Thorand, Harald Grallert, Christian Gieger, Michael Stumvoll, Frank Beutner, Inga Prokopenko, Matthias Blüher, Mathias Fasshauer, Holger Kirsten, Wolfgang Rathmann, Joachim Thiery, Kerstin Krause, Markus Scholz, Dorit Schleinitz, Carola Marzi, Anke Tönjes, Arnd Gross, Leif Groop, Jennifer Kriebel, Jürgen Kratzsch, Claes Ladenvall, Bo Isomaa |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.medical_specialty Linkage disequilibrium lcsh:QH426-470 Gene Identification and Analysis Subcutaneous Fat Adipokine Adipose tissue Gene Expression Single-nucleotide polymorphism Genome-wide association study Quantitative trait locus Endocrinology and Diabetes Intra-Abdominal Fat Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine Genetics Medicine and Health Sciences Diabetes Mellitus Chemerin Humans Genetic Predisposition to Disease Obesity Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics 030304 developmental biology Genetic association 2. Zero hunger Diabetic Endocrinology 0303 health sciences biology Biology and Life Sciences 3. Good health lcsh:Genetics Metabolic Disorders biology.protein Intercellular Signaling Peptides and Proteins Chemokines 030217 neurology & neurosurgery Research Article Genome-Wide Association Study |
| Zdroj: | PLoS Genetics, Vol 10, Iss 12, p e1004854 (2014) PLoS Genetics e1004854 PLoS Genet. 10:e1004854 (2015) PLoS Genetics; 10(12), no e1004854 (2014) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | 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 Author Summary Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. In the present study we show that circulating chemerin is a heritable trait. In a meta-analysis of genome-wide association studies (GWAS) of 2,791 individuals from Germany and Finland, we identified common genetic variants which associate with serum chemerin levels. The variants map within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) at chromosome 7. To better understand the potential functionality of the identified variants, we also provide insights into the mRNA expression of RARRES2 (encoding chemerin) in blood and adipose tissue. Our results highlight the role and function of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations. |
| Databáze: | OpenAIRE |
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