Sleep and Fatigue Scores Differ Between Cytokine Genotypes in Young People With Crohnʼs Disease

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Introduction: Sleep disturbances and fatigue are among the most frequent and impairing symptoms in young people with Crohn's disease. Several clinical characteristics have been identified to contribute to variability in sleep disturbances and fatigue; yet, less is known about the contributions of biological mechanisms in this population. Inflammatory processes are involved in the development of these symptoms, however, no studies have evaluated for associations between polymorphisms in genes involved in inflammation and sleep disturbances or fatigue in Crohn's disease. The purpose of this exploratory study was to identify differences in self-reports of sleep quality and fatigue between cytokine genotypes in adolescents and young adults with Crohn's disease. Methods: Participant reports of sleep quality and fatigue were collected using the Pittsburgh Sleep Quality Index (PSQI) and Multidimensional Fatigue Inventory (MFI), respectively. We selected 20 functional SNPs in 9 cytokine genes to evaluate in this study. These genes have been linked to variability in sleep and fatigue in other chronic conditions. Genotype data was collected using either the Sequenom iPLEX MassArray platform or Taqman Genotyping Assays. Differences between genotypes of each SNP and PSQI and MFI scores were independently evaluated using t-tests. Results: Data from 42 participants (mean age: 23.9 years; 62% female) were included in this study. Participants who had one or two doses of the minor allele for NFKB2 rs12772374 (t(39)=-2.57, p=.014) and TNFA rs361525 (t(39)=-2.53, p=.016) had significantly poorer sleep quality than those homozygous wildtype. Likewise, participants who had one or two doses of the minor allele for IL-10 rs1800871 (t(40)= -2.14, p=.039), and TNFA rs3093662 (t(40)=-2.18, p=.035) had significantly worse fatigue than those homozygous wildtype. Participants who were homozygous wildtype for IL-10 rs1878672 had significantly worse fatigue than those with the presence of the minor allele (t(40)= 2.80, p=.008). Conclusion: This study identified the minor allele in several SNPs in cytokine genes likely contribute to the variability in sleep quality or fatigue. These SNPs have known consequences on associated gene products and could potentially serve as a stable biomarker to identify people at risk for poor sleep or fatigue and targets for pharmacological or non-pharmacologic interventions. Further investigation is necessary to confirm and extend findings in a larger sample.733_A Figure 1 No Caption available.733_B Figure 2 No Caption available.