Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome

Abstract

BACKGROUND: Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients  suffer from sustained exhaustion, cognitive impairment and an increased  sensitivity to pain and sensory stimuli. A subset of patients has frequent  respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous  system and an association with genetic variations in the  catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing  sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed  the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in  CFS patients and correlated them to immunoglobulin levels and susceptibility to  RRTI. METHODS: We analyzed blood cells of 74 CFS patients and 76 healthy controls  for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum  immunoglobulins were determined by immunoturbidimetric technique, cortisol levels  by ECLIA. RESULTS: Contrary to previous reports, we found no difference between  CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and  CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced  cortisol levels providing evidence for its functional relevance. Both enhanced  IgE and diminished IgG3 levels and an increased susceptibility to RRTI were  observed in CFS patients with the Met/Met variant. Such an association was not  observed in 68 non-CFS patients with RRTI. CONCLUSION: Our results indicate a  relationship of COMT polymorphism rs4680 with immune dysregulation in CFS  providing a potential link for the association between stress and infection  susceptibility in CFS.