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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

Correlation of IgE levels with COMT SNP rs4680. Serum of 54 CFS patients was analyzed for IgE. Patients were group in either Met/Met, Met/Val, or the wild type variant Val/Val. Enhanced IgE levels are defined >100 U/ml (dashed line). Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between Met/Met or Met/Val and the variant Val/Val.
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Fig3: Correlation of IgE levels with COMT SNP rs4680. Serum of 54 CFS patients was analyzed for IgE. Patients were group in either Met/Met, Met/Val, or the wild type variant Val/Val. Enhanced IgE levels are defined >100 U/ml (dashed line). Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between Met/Met or Met/Val and the variant Val/Val.

Mentions: Furthermore, it had been shown that norepinephrine upregulates IgE production [32]. Thus, we compared COMT subgroups in 54 CFS patients whose IgE levels had been determined. Indeed, we found that all 10 patients with enhanced IgE levels, defined as above 100 U/ml, had hetero- or homozygous Met allele (n = 10/44, 22.7 %) whereas no patient (n = 0/10) was found in the Val/Val group (Fig. 3). Of those 10 patients with elevated IgE, 7 patients had reported allergies.Fig. 3


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)

Correlation of IgE levels with COMT SNP rs4680. Serum of 54 CFS patients was analyzed for IgE. Patients were group in either Met/Met, Met/Val, or the wild type variant Val/Val. Enhanced IgE levels are defined >100 U/ml (dashed line). Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between Met/Met or Met/Val and the variant Val/Val.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Correlation of IgE levels with COMT SNP rs4680. Serum of 54 CFS patients was analyzed for IgE. Patients were group in either Met/Met, Met/Val, or the wild type variant Val/Val. Enhanced IgE levels are defined >100 U/ml (dashed line). Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between Met/Met or Met/Val and the variant Val/Val.
Mentions: Furthermore, it had been shown that norepinephrine upregulates IgE production [32]. Thus, we compared COMT subgroups in 54 CFS patients whose IgE levels had been determined. Indeed, we found that all 10 patients with enhanced IgE levels, defined as above 100 U/ml, had hetero- or homozygous Met allele (n = 10/44, 22.7 %) whereas no patient (n = 0/10) was found in the Val/Val group (Fig. 3). Of those 10 patients with elevated IgE, 7 patients had reported allergies.Fig. 3

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