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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

Distribution of variants for COMT rs4680 in 34 CFS patients with RRTI and 40 CFS patients without RRTI. As control 68 non-CFS patients with RRTI were analysed. Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between the variant Met/Met and Met/Val, and the major variant Val/Val.
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Fig4: Distribution of variants for COMT rs4680 in 34 CFS patients with RRTI and 40 CFS patients without RRTI. As control 68 non-CFS patients with RRTI were analysed. Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between the variant Met/Met and Met/Val, and the major variant Val/Val.

Mentions: As a subset of patients with CFS suffers from susceptibility to infections, we analyzed if COMT SNPs are associated with infections. 34 of the 74 patients reported to suffer from RRTI. The clinical characteristics of the patient cohort are shown in Table 3. 47 % of CFS patients with RRTI had received antibiotic treatment for RRTI. There was no significant difference in median ages, gender or Bell score between the two groups with and without RRTI. Interestingly, we found that RRTI are significantly more frequent in the presence of the Met variant of SNP rs4680 for COMT in the CFS patients (Fig. 4, p = 0.023). While 31 (91 %) of the 34 patients with RRTI had Met, 28 of 40 (70 %) patients without RRTI had a Met allele. In contrast, no association was observed for the SNPs for FKBP5 rs1360780 and CRHR1 rs12944712.Table 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)

Distribution of variants for COMT rs4680 in 34 CFS patients with RRTI and 40 CFS patients without RRTI. As control 68 non-CFS patients with RRTI were analysed. Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between the variant Met/Met and Met/Val, and the major variant Val/Val.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Distribution of variants for COMT rs4680 in 34 CFS patients with RRTI and 40 CFS patients without RRTI. As control 68 non-CFS patients with RRTI were analysed. Statistic analysis was performed with two-tailed Chi-Square/Fisher’s exact test with *p < 0.05 between the variant Met/Met and Met/Val, and the major variant Val/Val.
Mentions: As a subset of patients with CFS suffers from susceptibility to infections, we analyzed if COMT SNPs are associated with infections. 34 of the 74 patients reported to suffer from RRTI. The clinical characteristics of the patient cohort are shown in Table 3. 47 % of CFS patients with RRTI had received antibiotic treatment for RRTI. There was no significant difference in median ages, gender or Bell score between the two groups with and without RRTI. Interestingly, we found that RRTI are significantly more frequent in the presence of the Met variant of SNP rs4680 for COMT in the CFS patients (Fig. 4, p = 0.023). While 31 (91 %) of the 34 patients with RRTI had Met, 28 of 40 (70 %) patients without RRTI had a Met allele. In contrast, no association was observed for the SNPs for FKBP5 rs1360780 and CRHR1 rs12944712.Table 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