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

Löbel M, Mooslechner AA, Bauer S, Günther S, Letsch A, Hanitsch LG, Grabowski P, Meisel C, Volk HD, Scheibenbogen C - J Transl Med (2015)

Bottom Line: 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.Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Campus Virchow, Augustenburger Platz 1/Südstraße 2, 13353, Berlin, Germany. madlen.loebel@charite.de.

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.

No MeSH data available.


Related in: MedlinePlus

Cortisol levels in CFS patients. Serum of 55 CFS patients was analyzed for cortisol levels. Patients were grouped in the respective haplotypes of the SNPs for a rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1. Statistic analysis was performed with the Kruskal–Wallis test followed by post hoc testing via two-tailed Mann–Whitney U test with Bonferroni adjustment for multiple testing with ***p < 0.00033 (0.001/3 comparisons) as significant, ns not significant.
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Fig1: Cortisol levels in CFS patients. Serum of 55 CFS patients was analyzed for cortisol levels. Patients were grouped in the respective haplotypes of the SNPs for a rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1. Statistic analysis was performed with the Kruskal–Wallis test followed by post hoc testing via two-tailed Mann–Whitney U test with Bonferroni adjustment for multiple testing with ***p < 0.00033 (0.001/3 comparisons) as significant, ns not significant.

Mentions: To assess the functional relevance of the SNPs, cortisol levels were compared in the groups of CFS patients with wild type, heterozygous and homozygous variants. We found significantly enhanced cortisol levels in the group of CFS patients with the Met/Met allele compared to heterozygous and Val/Val allele carrying patients (Fig. 1a). In contrast no association was found for cortisol levels and SNPs for FKBP5 and CRHR1 (Fig. 1b, c).Fig. 1


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

Löbel M, Mooslechner AA, Bauer S, Günther S, Letsch A, Hanitsch LG, Grabowski P, Meisel C, Volk HD, Scheibenbogen C - J Transl Med (2015)

Cortisol levels in CFS patients. Serum of 55 CFS patients was analyzed for cortisol levels. Patients were grouped in the respective haplotypes of the SNPs for a rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1. Statistic analysis was performed with the Kruskal–Wallis test followed by post hoc testing via two-tailed Mann–Whitney U test with Bonferroni adjustment for multiple testing with ***p < 0.00033 (0.001/3 comparisons) as significant, ns not significant.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536662&req=5

Fig1: Cortisol levels in CFS patients. Serum of 55 CFS patients was analyzed for cortisol levels. Patients were grouped in the respective haplotypes of the SNPs for a rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1. Statistic analysis was performed with the Kruskal–Wallis test followed by post hoc testing via two-tailed Mann–Whitney U test with Bonferroni adjustment for multiple testing with ***p < 0.00033 (0.001/3 comparisons) as significant, ns not significant.
Mentions: To assess the functional relevance of the SNPs, cortisol levels were compared in the groups of CFS patients with wild type, heterozygous and homozygous variants. We found significantly enhanced cortisol levels in the group of CFS patients with the Met/Met allele compared to heterozygous and Val/Val allele carrying patients (Fig. 1a). In contrast no association was found for cortisol levels and SNPs for FKBP5 and CRHR1 (Fig. 1b, c).Fig. 1

Bottom Line: 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.Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Campus Virchow, Augustenburger Platz 1/Südstraße 2, 13353, Berlin, Germany. madlen.loebel@charite.de.

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.

No MeSH data available.


Related in: MedlinePlus