No evidence of association between adrenocorticotropic hormone receptor promoter polymorphism and somatoform disorders

Somatization symptoms are frequently associated with feelings of distress, and these features interact with the activity of cortisol. Clinical studies indicate that hypocortisolism is a biological marker of stress-related disorders (Heim et al., 2000; Ehlert et al., 2001). We have described an adrenocorticotropic hormone (ACTH) receptor promoter polymorphism (-2 CTC→CCC) within the transcription initiation site that leads to a lower ACTH sensitivity in normal individuals (Slawik et al., 2004), which is associated with a lower cortisol secretion (Reisch et al., 2005) and therefore may influence cortisol homeostasis under stress conditions. The aim of this cross-sectional study was therefore to investigate the prevalence of the -2 CTC→CCC ACTH receptor promoter polymorphism systematically in a group of patients with SFD (somatoform disorders). Blood samples of 42 patients (33 women, nine men with an age range of 18-63 years; median 40.5) who met International Classification of Diseases-10 diagnostic criteria for SFD were analyzed for the ACTH receptor promoter polymorphism as previously described (Slawik et al., 2004) and compared with male healthy control individuals (n=1.266 with an age range of 18-50). All patients (recruited from the Psychosomatic Outpatient Clinic) and healthy controls (recruited from blood donors) were German with a European genetic background. In SFD, 35 patients revealed the wild-type genotype (83%), six were heterozygous (14%) and one homozygous (2%) for the -2 CTC→CCC ACTH receptor promoter polymorphism. The prevalence of the polymorphism in 1266 unrelated healthy men was 80.2% for CTC/CTC, 19.0% for CTC/CCC, and 0.8% for CCC/CCC (genotypes were in Hardy-Weinberg equilibrium). The prevalence of the -2 CTC→CCC ACTH receptor promoter polymorphism in SFD did not differ from the normal healthy population (P=0.298). Additionally, we found only moderate depression severity scores (Hamilton Depression Rating Scale 14.0, SD=6.44; Beck Depression Inventory 18.6, SD=10.71) and no significant relationship between the carrier status of the -2 CTC→CCC ACTH receptor promoter polymorphism (wild type or heterozygous/homozygous) and the depression scores [Hamilton Depression Rating Scale (P=0.950, d.f.=40) and Beck Depression Inventory (P=0.934, d.f.=40)]. The hypocortisolism of stress-related disorders such as SFD described in recent studies (e.g. Heim et al., 2000) obviously can not be explained by a decreased adrenal responsiveness to ACTH resulting in lower cortisol secretion owing to the -2 CTC→CCC polymorphism within the transcription initiation site of the ACTH receptor gene. In summary, our results do not support an involvement of the -2 CTC→CCC ACTH receptor promoter polymorphism in SFD; further studies would be valuable to replicate our results. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.