title: A polymorphism in the 5' untranslated region of the human ob gene is associated with low leptin levels.
abstract: OBJECTIVE
  To search the human ob gene for mutations and evaluate their role in massive obesity.
  
  
  METHODS
  Direct mutation screening of the gene and case-control association study. Multivariate analyses for evaluation of differences in clinical parameters.
  
  
  METHODS
  Primary mutation screening: 24 morbidly obese subjects (body mass index (BMI) > 40 kg/m2). Association study: 395 unrelated morbidly obese subjects (BMI > 40 kg/m2), 121 lean, non-diabetic control individuals, 72 women of a random sample with an average BMI 32.5 kg/m2.
  
  
  RESULTS
  We report the finding of a DNA variant in exon 1 of the human ob gene (A --> G substitution, base + 19). This variant showed a prevalence of 62% in our study population. Association analyses under different genetic models (dominant, co-dominant, recessive) showed no significant evidence for an association of this variant with BMI. However, obese individuals homozygous for the G-allele showed significantly lower leptin concentrations compared to obese patients either heterozygous or homozygous for the A-allele after correction for BMI.
  
  
  CONCLUSIONS
  Recent linkage studies have shown evidence for linkage of the hsob locus with obesity. Our study provides further evidence that a defect in the ob gene in linkage disequilibrium with the G-allele of exon 1 might be involved in obesity by affecting leptin concentrations.
authors.affiliation: CNRS EP10 Institut Pasteur de Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Hager
authors.forename: K
authors.initials: K
authors.lastname: Clement
authors.forename: S
authors.initials: S
authors.lastname: Francke
authors.forename: C
authors.initials: C
authors.lastname: Dina
authors.forename: J
authors.initials: J
authors.lastname: Raison
authors.forename: N
authors.initials: N
authors.lastname: Lahlou
authors.forename: N
authors.initials: N
authors.lastname: Rich
authors.forename: V
authors.initials: V
authors.lastname: Pelloux
authors.forename: A
authors.initials: A
authors.lastname: Basdevant
authors.forename: B
authors.initials: B
authors.lastname: Guy-Grand
authors.forename: M
authors.initials: M
authors.lastname: North
authors.forename: P
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005838:Genotype; D006801:Humans; D020738:Leptin; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009767:Obesity, Morbid / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics; D011506:Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D017931:DNA Primers; D020738:Leptin; D011506:Proteins