PMID: 9539186Apr 16, 1998Paper

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

International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity
J HagerP Froguel

Abstract

To search the human ob gene for mutations and evaluate their role in massive obesity. Direct mutation screening of the gene and case-control association study. Multivariate analyses for evaluation of differences in clinical parameters. 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. 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. 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 e...Continue Reading

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