Association of a polymorphism in the H6PD gene and basal cortisol secretion, body fat mass and leptin level (Assoziation eines Polymorphismus im H6PD Gen mit basaler Cortisolsekretion, Fettmasse und Leptinwerten)

Bellingrath, Silja, Kumsta, Robert, Meyer, Jobst, Moser, Dirk, Federenko, Ilona S., Hellhammer, Dirk H. and Wüst, Stefan (2005) Association of a polymorphism in the H6PD gene and basal cortisol secretion, body fat mass and leptin level (Assoziation eines Polymorphismus im H6PD Gen mit basaler Cortisolsekretion, Fettmasse und Leptinwerten). Zeitschrift für Medizinische Psychologie, 14 (3), 111-117.

Abstract

The hypothalamus-pituitary-adrenal (HPA) axix is vital for an organism's response to physical or psychosocial stimulation. Chronic dysregulation of HPA axis activity is related to several psychiatric and psychosomatic disorders. Cortisol, the end product of this endocrine system, affects a multitude of systems in the body, including the HPA axis itself and it also has an influence on behavior. The intracellular availability of cortisol is crucial for the regulation of this endocrine system. The enzyme hexose-6-phosphat-dehydrogenase (H6PDH) affects cortisol availability via its influenec on 11?-hydroxysteroid dehydrogenase type I (11?-HSDI)-activity, which regenerates cortisol from inactive cortisone. 116 healthy males (33 monozygotic & 25 dizygotic twin pairs) were studied to estimate the association between a polymorphism in the exon 5 of the H6PD gene (R435Q, GA) and adrenocortical responses to psychosocial stress, basal salivary cortisol levels and body composition. Compared with subjects with the more frequent H6PD genotypers the homozygous AA-carriers displayed a significantly decreased cortisol awakening rise (CAR) as well as lower daytime cortisol levels. In response to stress, the AA-carriers exhibited a trend towards lower cortisol and ACH responses compared with GG- and GA-carriers. In addition, significantly higher levels of leptin and amount of body fat were observed in AA-carriers. We hypothesize that the R453Q polymorphism in the H6PD gene might influence intracellular cortisol availability and thus affect HPA axis regulation.

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