title: Fat depot-specific mRNA expression of novel loci associated with waist-hip ratio.
abstract: OBJECTIVE
  We hypothesized that genes within recently identified loci associated with waist-hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits.
  
  
  METHODS
  Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3 and GRB14) within these loci showing coincident cis-expression quantitative trait loci was measured in 222 paired samples of human visceral (vis) and subcutaneous (sc) AT. The relationship of mRNA expression levels with obesity-related quantitative traits was assessed by Pearson's correlation analyses. Multivariate linear relationships were assessed by generalized linear regression models.
  
  
  RESULTS
  Whereas only PIGC, ZNFR3 and STAB1 mRNA expression in sc AT correlated nominally with WHR (P<0.05, adjusted for age and sex), mRNA expression of all studied genes in at least one of the fat depots correlated significantly with vis and/or sc fat area (P ranging from 0.05 to 4.0 × 10(6), adjusted for age and sex). Consistently, the transcript levels of WARS, PIGC and GRB14 were nominally associated with body mass index (BMI) (P ranging from 0.02 to 9.2 × 10(5), adjusted for age and sex). Moreover, independent of sex, obesity and diabetes status, differential expression between vis and sc AT was observed for all tested genes (P<0.01). Finally, the rs10195252 T-allele was nominally associated with increased GRB14 sc mRNA expression (P=0.025 after adjusting for age, sex and BMI).
  
  
  CONCLUSIONS
  Our data including the inter-depot variability of mRNA expression suggests that genes within the WHR-associated loci might be involved in the regulation of fat distribution.
authors.affiliation: Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schleinitz
authors.affiliation: 1] Department of Internal Medicine, Neurology, and Dermatology, Clinic for Endocrinology and Nephrology, University Clinic of Leipzig, Leipzig, Germany [2] IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Klöting
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Lindgren
authors.affiliation: Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Breitfeld
authors.affiliation: 1] Department of Internal Medicine, Neurology, and Dermatology, Clinic for Endocrinology and Nephrology, University Clinic of Leipzig, Leipzig, Germany [2] IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dietrich
authors.affiliation: Municipal Clinic Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, Germany.
authors.forename: M R
authors.initials: MR
authors.lastname: Schön
authors.affiliation: Municipal Clinic, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Lohmann
authors.affiliation: Municipal Clinic, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dreßler
authors.affiliation: 1] Department of Internal Medicine, Neurology, and Dermatology, Clinic for Endocrinology and Nephrology, University Clinic of Leipzig, Leipzig, Germany [2] IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK [3] Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
authors.affiliation: Department of Internal Medicine, Neurology, and Dermatology, Clinic for Endocrinology and Nephrology, University Clinic of Leipzig, Leipzig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Kovacs
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001823:Body Composition; D050218:Body Fat Distribution; D015992:Body Mass Index; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014369:Tryptophan-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D049629:Waist-Hip Ratio
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; C099655:GRB14 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; C449926:STAB1 protein, human; D020825:T-Box Domain Proteins; C523795:TBX15 protein, human; D044767:Ubiquitin-Protein Ligases; C572950:ZNRF3 protein, human; D006602:Hexosyltransferases; C101351:PIGC protein, human; D014369:Tryptophan-tRNA Ligase; C073175:WARS1 protein, human