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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 CFS patients with COMT, FKBP5, and CRHR1 SNP. a Levels of immunoglobulin subclasses IgG3 and IgG4 were determined in serum of CFS patients and grouped according to their genotype for rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1, respectively. 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 < 0.017 (0,05/3 comparisons) as significant.
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Fig2: IgG3 and IgG4 levels in CFS patients with COMT, FKBP5, and CRHR1 SNP. a Levels of immunoglobulin subclasses IgG3 and IgG4 were determined in serum of CFS patients and grouped according to their genotype for rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1, respectively. 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 < 0.017 (0,05/3 comparisons) as significant.

Mentions: We had observed that a subset of CFS patients has diminished IgG3 and IgG4 levels. Due to the known effect of stress and cortisol on immunoglobulin levels [30, 31] we therefore correlated the haplotypes for the SNPs for COMT, FKBP5 and CRHR1 with the patient’s IgG3 and IgG4 levels. Interestingly, we found that the homozygous and heterozygous Met variant of COMT rs4680 is associated with significantly lower IgG3 levels in comparison to the homozygous Val genotype (Fig. 2a). No difference for the other IgG subclasses as well as IgG, IgM, and IgA was observed (data not shown). Oppositely, in patients with the FKBP5 SNP rs1360780 wild type variant C/C significantly lower levels of IgG4 were found compared to the C/T or T/T variant, but no differences in the IgG3 levels (Fig. 2b). However, the differences in IgG4 were no longer significant after Bonferroni correction. No differences were found for the CRHR1 SNP rs12944712 (A/A, A/G, G/G) and IgG3/4 levels (Fig. 2c).Fig. 2


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 CFS patients with COMT, FKBP5, and CRHR1 SNP. a Levels of immunoglobulin subclasses IgG3 and IgG4 were determined in serum of CFS patients and grouped according to their genotype for rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1, respectively. 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 < 0.017 (0,05/3 comparisons) as significant.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: IgG3 and IgG4 levels in CFS patients with COMT, FKBP5, and CRHR1 SNP. a Levels of immunoglobulin subclasses IgG3 and IgG4 were determined in serum of CFS patients and grouped according to their genotype for rs4680 for COMT, b rs1360780 for FKBP5, and c rs12944712 for CRHR1, respectively. 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 < 0.017 (0,05/3 comparisons) as significant.
Mentions: We had observed that a subset of CFS patients has diminished IgG3 and IgG4 levels. Due to the known effect of stress and cortisol on immunoglobulin levels [30, 31] we therefore correlated the haplotypes for the SNPs for COMT, FKBP5 and CRHR1 with the patient’s IgG3 and IgG4 levels. Interestingly, we found that the homozygous and heterozygous Met variant of COMT rs4680 is associated with significantly lower IgG3 levels in comparison to the homozygous Val genotype (Fig. 2a). No difference for the other IgG subclasses as well as IgG, IgM, and IgA was observed (data not shown). Oppositely, in patients with the FKBP5 SNP rs1360780 wild type variant C/C significantly lower levels of IgG4 were found compared to the C/T or T/T variant, but no differences in the IgG3 levels (Fig. 2b). However, the differences in IgG4 were no longer significant after Bonferroni correction. No differences were found for the CRHR1 SNP rs12944712 (A/A, A/G, G/G) and IgG3/4 levels (Fig. 2c).Fig. 2

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