Mental quality of life is related to a cytokine genetic pathway.
BACKGROUND
Quality of life (QoL) in patients with chronic disease is impaired and cannot be solely explained by disease severity. We explored whether genetic variability and activity contributes to QoL in patients with Marfan syndrome (MFS), a genetic connective tissue disorder.


RESULTS
In 121 MFS patients, patient characteristics (i.e. demographics and MFS-related symptoms) were assessed. Patients completed the SF-36 to measure QoL. In addition, transcriptome wide gene expression and 484 Single Nucleotide Polymorphysms (SNPs) in cytokine genes were available. QoL was first analyzed and associated with patient characteristics. Patients' physical QoL was impaired and weakly related with age and scoliosis, whereas mental quality of life (MCS) was normal. To explain a largely lacking correlation between disease severity and QoL, we related genome wide gene expression to QoL. Patients with lower MCS scores had high expression levels of CXCL9 and CXCL11 cytokine-related genes (p=0.001; p=0.002); similarly, patients with low vitality scores had high expression levels of CXCL9, CXCL11 and IFNA6 cytokine-related genes (p=0.02; p=0.02; p=0.04), independent of patient characteristics. Subsequently, we associated cytokine related SNPs to mental QoL (MCS and vitality). SNP-cluster in the IL4R gene showed a weak association with MCS and vitality (strongest association p=0.0017). Although overall mental QoL was normal, >10% of patients had low scores for MCS and vitality. Post-hoc analysis of systemic inflammatory mediators showed that patients with lowest MCS and vitality scores had high levels of CCL11 cytokine (p=0.03; p=0.04).


CONCLUSIONS
Variation in the cytokine genetic pathway and its activation is related to mental QoL. These findings might allow us to identify and, ultimately, treat patients susceptible to poor QoL.
Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands.
Dounya
D
Schoormans
Teodora
T
Radonic
Piet
P
de Witte
Maarten
M
Groenink
Donija
D
Azim
Rene
R
Lutter
Barbara J M
BJ
Mulder
Mirjam A G
MA
Sprangers
Aeilko H
AH
Zwinderman
D000328:Adult; D054371:Chemokine CXCL11 / Q000235:genetics*; D054370:Chemokine CXCL9 / Q000235:genetics; D002908:Chronic Disease; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D008603:Mental Health; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011788:Quality of Life; D015398:Signal Transduction; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D059467:Transcriptome / Q000235:genetics*
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; C554163:IFNA6 protein, human; C504000:IL4R protein, human; D016898:Interferon-alpha; D053662:Interleukin-4 Receptor alpha Subunit