A polymorphism in the 5' untranslated region of the human ob gene is associated with low leptin levels

Int J Obes Relat Metab Disord. 1998 Mar;22(3):200-5. doi: 10.1038/sj.ijo.0800567.


Objective: To search the human ob gene for mutations and evaluate their role in massive obesity.

Design: Direct mutation screening of the gene and case-control association study. Multivariate analyses for evaluation of differences in clinical parameters.

Subjects: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Case-Control Studies
  • Cohort Studies
  • DNA Primers / chemistry
  • Female
  • Genotype
  • Humans
  • Leptin
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics*
  • Obesity, Morbid / blood
  • Obesity, Morbid / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Protein Biosynthesis / genetics
  • Proteins / analysis
  • Proteins / genetics*


  • DNA Primers
  • Leptin
  • Proteins