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Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin
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نویسنده
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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. ,thiery j. ,fasshauer m. ,klöting n. ,gieger c. ,blüher m. ,stumvoll m. ,kovacs p.
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منبع
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plos genetics - 2014 - دوره : 10 - شماره : 12
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چکیده
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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. © 2014 tönjes et al.
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آدرس
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department of medicine,university of leipzig,leipzig, Germany, institute of medical informatics,statistics and epidemiology,university of leipzig,leipzig,germany,life research center,university of leipzig,leipzig, Germany, ifb adiposity diseases,university of leipzig,leipzig, Germany, research unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg,germany,institute of epidemiology ii,helmholtz center munich,german research center for environmental health,neuherberg,germany,german center for diabetes research (dzd e.v.),neuherberg, Germany, research unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg,germany,institute of epidemiology ii,helmholtz center munich,german research center for environmental health,neuherberg,germany,german center for diabetes research (dzd e.v.),neuherberg, Germany, institute of medical informatics,statistics and epidemiology,university of leipzig,leipzig,germany,life research center,university of leipzig,leipzig, Germany, department of clinical sciences,diabetes and endocrinology,lund university and lund university diabetes centre,crc at skåne university hospital,malmö, Sweden, department of medicine,university of leipzig,leipzig, Germany, department of medicine,university of leipzig,leipzig, Germany, institute of medical informatics,statistics and epidemiology,university of leipzig,leipzig,germany,life research center,university of leipzig,leipzig,germany,department for cell therapy,fraunhofer institute for cell therapy and immunology,leipzig, Germany, department of clinical sciences,diabetes and endocrinology,lund university and lund university diabetes centre,crc at skåne university hospital,malmö, Sweden, research unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg,germany,institute of epidemiology ii,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of epidemiology ii,helmholtz center munich,german research center for environmental health,neuherberg,germany,institute of epidemiology ii,helmholtz zentrum münchen,german research center for environmental health,münchen, Germany, institute of biometrics and epidemiology,german diabetes center,leibniz center for diabetes research at heinrich heine university düsseldorf,düsseldorf, Germany, department of clinical sciences,diabetes and endocrinology,lund university and lund university diabetes centre,crc at skåne university hospital,malmö, Sweden, wellcome trust centre for human genetics,university of oxford,oxford,united kingdom,oxford centre for diabetes,endocrinology and metabolism,university of oxford,oxford,united kingdom,department of genomics of common diseases,imperial college london,london, United Kingdom, department of social services and health care,jakobstad,finland,folkhälsan research centre,helsinki, Finland, institute of laboratory medicine,clinical chemistry and molecular diagnostics,university hospital leipzig,leipzig, Germany, institute of laboratory medicine,clinical chemistry and molecular diagnostics,university hospital leipzig,leipzig, Germany, institute of laboratory medicine,clinical chemistry and molecular diagnostics,university hospital leipzig,leipzig, Germany, department of medicine,university of leipzig,leipzig,germany,ifb adiposity diseases,university of leipzig,leipzig, Germany, department of medicine,university of leipzig,leipzig,germany,ifb adiposity diseases,university of leipzig,leipzig, Germany, institute of genetic epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, department of medicine,university of leipzig,leipzig,germany,ifb adiposity diseases,university of leipzig,leipzig, Germany, department of medicine,university of leipzig,leipzig,germany,ifb adiposity diseases,university of leipzig,leipzig, Germany, ifb adiposity diseases,university of leipzig,leipzig, Germany
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Authors
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