title: Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23.
abstract: BACKGROUND
  There is evidence that one of the key type 2 diabetes (T2D) loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX), insulin-degrading enzyme (IDE) and kinesin family member 11 (KIF11), respectively.
  
  
  METHODS
  We analyzed the impact of adipogeneis on the mRNA and protein expression levels of these genes in the human adipocyte Simpson-Golabi-Behmel syndrome (SGBS) cell line in order to investigate which could be the culprit gene(s) in this region of linkage disequilibrium.
  
  
  RESULTS
  Following activation of differentiation with a PPARγ ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of 80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte states. We also observed decreases in KIF11 and IDE protein levels, but conversely we observed a dramatic increase in HHEX protein levels. Subsequent time course experiments revealed some marked changes in expression as early as three hours after activation of differentiation.
  
  
  CONCLUSIONS
  Our data suggest that the expression of all three genes at this locus are impacted during SGBS adipogenesis and provides insights in to the possible mechanisms of how the genes at this 10q23 locus could influence both adipocyte differentiation and susceptibility to T2D through insulin resistance.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
authors.forename: Sandra
authors.initials: S
authors.lastname: Deliard
authors.forename: Ali Rahim
authors.initials: AR
authors.lastname: Aziz
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D001145:Arrhythmias, Cardiac / Q000235:genetics; D015992:Body Mass Index; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020869:Gene Expression Profiling; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005877:Gigantism / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics; D007339:Insulysin / Q000096:biosynthesis; D008607:Intellectual Disability / Q000235:genetics; D016547:Kinesins / Q000096:biosynthesis; D015810:Linkage Disequilibrium / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis; D000077288:Troglitazone
chemical_list: D002839:Chromans; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; C470243:KIF11 protein, human; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D007339:Insulysin; D016547:Kinesins; D000077288:Troglitazone