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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

IgG3 and IgG4 levels in 68 non-CFS patients with RRTI with COMT and FKBP5 SNP. 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.
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Fig5: IgG3 and IgG4 levels in 68 non-CFS patients with RRTI with COMT and FKBP5 SNP. 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.

Mentions: To study if this association of Met with RRTI was seen in non-CFS patients as well we analyzed an additional cohort of 68 patients, who had presented due to RRTI at our outpatient clinic (patient characteristics shown in Table 3) for the prevalence of these COMT variants. In this cohort the frequency of the Met variant was similar to CFS patients without RRTI (71 %). Further, neither an association of COMT variants with IgG3 and IgG4 levels (Fig. 5) nor with IgE levels (not shown) was found.Fig. 5


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)

IgG3 and IgG4 levels in 68 non-CFS patients with RRTI with COMT and FKBP5 SNP. 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.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: IgG3 and IgG4 levels in 68 non-CFS patients with RRTI with COMT and FKBP5 SNP. 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.
Mentions: To study if this association of Met with RRTI was seen in non-CFS patients as well we analyzed an additional cohort of 68 patients, who had presented due to RRTI at our outpatient clinic (patient characteristics shown in Table 3) for the prevalence of these COMT variants. In this cohort the frequency of the Met variant was similar to CFS patients without RRTI (71 %). Further, neither an association of COMT variants with IgG3 and IgG4 levels (Fig. 5) nor with IgE levels (not shown) was found.Fig. 5

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