Abstract

Background: Chronic fatigue syndrome is a complex and debilitating disorder. Several clinical studies suggest dysregulation of the hypothalamic-pituitary-adrenal axis and perturbations of the immune and central nervous systems. In this study we esamined the association between serotonin transporter (SERT) and receptor 2A (HTR2A), Glycogen synthase kinase 3 beta (GSK3B) and Brain Derived N eurotrophic Factor (BDNF) genes polymorphisms and CFS, in order to describe genetic associations. Methods: The coding and untranslated regions of each gene examined were amplified by PCR-RFLP. Results: The 44% of the CFS patients presents depressive symptoms: in this subgroup the presence of female sex is significantly higher (88%) than in not depressed patients (35%) (P = 0.0002). The genotypic and allelic frequencies of the HTR2A -1438G / A polymorphism showed a statistically significant difference (P = 0.05): the AA genotype is more present in patients with depressive symptoms. In particular, the frequency of the AA genotype was higher in the depressed patients (48%) compared to the patients without depressive symptoms (21%). The crude odds ratio for the presence of CFS associated with depression in subjects bearing the homozygous AA genotype was 3.56 (95% CI, 1.13 - 11.17). Conclusions: References of increased promoter activity, mRNA, protein levels and receptor binding with this promoter polymorphism and the association of the A allele with CFS sustain a hyperactive serotonergic system in this disease. So we suppose that the neuroendocrine system remains an intriguing field of research in CFS. doi:10.4021/jnr86w

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