Background/Purpose:

FM is the chronic experience of body-wide pain, fatigue, cognitive dysfunction, and disordered sleep that occurs in the absence of any clear cause. Fatigue is a cause of significant morbidity and disability in FM. Most genomic studies in the FM population focus on pain symptoms. Only a few studies had investigated the fatigue experience in FM and no genomic studies investigated FM-specific fatigue symptoms. The purpose of this study is to identify genomic categories of fatigue in fibromyalgia (FM) and describe behavioral characteristics of these fatigue categories.

Methods: Under an active Medstar Research Institute protocol, FM participants diagnosed by 2010 diagnostic criteria and pain-free, race, age, and gender-matched controls were enrolled in the study. Participants completed questionnaires. RNA from peripheral blood samples collected using Paxgene tubes® were analyzed for differential gene expression using microarray technology with Affymetrix GeneChip® human genome U133 Plus 2.0. Cluster analysis was used to determine genotypic categories. The differences of symptoms between two clusters were analyzed by the analysis of variance (ANOVA).

Results: Thirty one Caucasian women diagnosed with FM, experiencing significant fatigue (MFI-general fatigue ≥ 13) and 20 pain and fatigue free, age-, race-, gender-matched controls were enrolled. Microarray data showed differential upregulated expression of centromere protein K (CENPK) gene after the probesets passed filtering criteria of 1% false discovery rate (FDR) and a slope of > log2 (over 2.0-fold change, p < 0.05). This CENPK gene is related to centromere function. Cluster analysis was conducted on the expressed genes from FM subjects which revealed two distinct clusters. Forty nine genes were differentially expressed over 2-fold change (p < 0.05) between the two clusters. One cluster showed significantly higher pain interference (p = 0.028) and higher depression (p = 0.027). Genes that upregulated in the high pain interference and high depression cluster include genes related to immune response, iron absorption and GABA transport. Genes related to calcium iron binding were differentially expressed in the other FM cluster with lower pain interference and depression.

Conclusion: Within FM women with high fatigue, there appears to be two distinct patterns of gene expression. These genomic patterns correspond with differences in behavioral characteristics. Further investigation of these genomic patterns may provide some insights into the mechanisms behind the relationship of fatigue with other FM behavioral symptoms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genomic-categories-of-fatigue-in-women-with-fibromyalgia/