Mental Quality of Life Is Related to a Cytokine Genetic Pathway

Abstract

BackgroundQuality 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.Methodology/Principal FindingsIn 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/SignificanceVariation 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.

Marfan Syndrome and Quality of Life in the GenTAC Registry

“…The PCS composite score of 42.3 is better than scores seen in previous smaller studies of MFS patents (Table 6), including scores of 34.7 in Foran (22 patients with MFS) (8) and 36 in Rand-Hendriksen (84 patients with MFS) (12), but lower than the composite score of 45.5 in Schoormans’s study (121 patients with MFS) (10). Despite small sample sizes, nearly all of the prior studies of MFS patients found a reduction in the PCS composite or in the 4 component subscales (5,8–10,12,13) Three of these studies used control groups derived from national datasets as comparators (8,10,12). Fusar-Poli et al found a reduction in MCS but not PCS, but their study was limited by a low response rate, with only 36 MFS patients enrolled out of 380 families who were approached (9).…”

“…In a study of 121 MFS patients, a low PCS and low subscale scores did not correlate with disease severity (10). Similarly, in a study of 857 MFS patients that used a nonvalidated questionnaire, 26.5% of the 857 respondents thought they were severely affected by MFS, which did not correlate with MFS severity (22).…”

“…The questionnaire is subdivided into the Physical Component Score (PCS) and Mental Component Score (MCS). Because previous studies found that MFS predominantly affected the PCS (8,10,12,13), we used the PCS of the SF-36 to assess health related QOL in patients with MFS, and we evaluated the association of QOL with self-reported demographic factors, health behaviors, physical impairments, clinical characteristics, and MFS severity.…”

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update

“…Moreover, polymorphisms of IL-10 were associated with depressed mood in patients attending their GP with acute infection [46] or who had end stage renal disease [47]. Moreover, patients with Marfan disease who reported the lowest levels of mental QOL could also be distinguished on the basis of high expression levels of CXCL11, a gene coding for cytokines [7]. …”

“…Multiple publications and studies ensued laying the groundwork for methodological approaches and identifying candidate molecular markers [e.g., 5–7]. Replication of preliminary work has been seen alongside new markers [8].…”