ObjectiveTo examine the influence of genetic factors on plasma leptin levels.Subjects and methodsWe measured plasma leptin levels, body mass index and body fat distribution in healthy young female monozygotic (n= 19) and dizygotic (n= 14) twins. The twin zygosity was verified by determination of short tandem repeat and amplified fragment length polymorphism systems. The genetic analysis included analysis of variance-based and maximum likelihood-based methods.ResultsPlasma leptin levels were correlated significantly with body mass index (r= 0.59,P< 0.001), waist circumference (r = 0.54,P< 0.001) and hip circumference (r= 0.63,P< 0.001), but not with age (r = −0.17) or the waist: hip ratio (r= 0.02). The heritability estimates derived from intraclass correlations were significant for body mass index (P= 0.001), waist circumference (P= 0.004), hip circumference (P= 0.01) and plasma leptin levels (P= 0.005), but not for the waist : hip ratio (P= 0.22). In the maximum likelihood-based path analysis, heritability was estimated at 79% for body mass index and at 73% for plasma leptin levels. After adjustment for body mass index, the heritability estimate for leptin levels from the model-fitting approach was 55%.ConclusionsGenetic factors are major determinants of plasma leptin levels in humans and may account for as much as half of the variance in leptin levels.