title: The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population.
abstract: BACKGROUND
  The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits.
  
  
  METHODS
  We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations.
  
  
  METHODS
  Body mass index (BMI), indices of insulin sensitivity and beta-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508.
  
  
  RESULTS
  Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99-2.11) and G/C: OR=1.37 (1.04-1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels.
  
  
  CONCLUSIONS
  We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.
authors.affiliation: Department of Laboratory Medicine, Paracelsus Private Medical University, Salzburg, Austria.
authors.forename: T K
authors.initials: TK
authors.lastname: Felder
authors.forename: H
authors.initials: H
authors.lastname: Oberkofler
authors.forename: R
authors.initials: R
authors.lastname: Weitgasser
authors.forename: V
authors.initials: V
authors.lastname: Mackevics
authors.forename: F
authors.initials: F
authors.lastname: Krempler
authors.forename: B
authors.initials: B
authors.lastname: Paulweber
authors.forename: W
authors.initials: W
authors.lastname: Patsch
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D001317:Austria / Q000453:epidemiology; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D052242:Adiponectin; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1