Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins

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Abstract

OBJECTIVE

The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors.

DESIGN

We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale.

RESULTS

Leptin and BMI showed substantial heritability (68·3% and 71·3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11β-hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5α-reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63·8% (P = 0·012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5α-reductase activity.

CONCLUSIONS

We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.

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