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) b 40 kg/m 2 ). Association study: 395 unrelated morbidly obese subjects (BMI b 40 kg/m 2 ), 121 lean, non-diabetic control individuals, 72 women of a random sample with an average BMI 32.5 kg/m 2 . RESULTS: We report the ®nding of a DNA variant in exon 1 of the human ob gene (A 7 bG 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 signi®cant evidence for an association of this variant with BMI. However, obese individuals homozygous for the G-allele showed signi®cantly 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.
The menopause is associated with changes in body composition: a decline in bone mineral content, a decrease in collagen synthesis, a loss of lean body mass and an increase in total and abdominal fat mass. Oestrogen deficiency seems to play a role in the menopause-related changes in body composition, but life styles (diet, exercise, smoking habits, alcohol consumption) are also involved. The time course of the decrease in lean mass deserves attention since it could justify specific actions, i.e. exercising or hormonal treatment, early during the perimenopausal period. A decrease in fat-free mass may be responsible for a decrease in energy expenditure favouring weight gain if the calorie intake is not reduced.
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