Genetic associations of fatigue and other symptom domains of the acute sickness response to infection

Piraino, B.; Vollmer‐Conna, Ute; Lloyd, Andrew R.

doi:10.1016/j.bbi.2011.12.009

Cited by 59 publications

(65 citation statements)

References 40 publications

(47 reference statements)

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“…For example, the allele of IL4 rs 2243248 was associated with high depression levels in oncology outpatients [44], and TNF-308 and IL6-174 polymorphisms that were found to be associated with fatigue were also associated with depression in breast cancer patients [45]. 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].…”

Section: Resultsmentioning

confidence: 99%

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

Sprangers

Thong

Bartels³

et al. 2014

Qual Life Res

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Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL.

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Section: Resultsmentioning

confidence: 99%

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

Sprangers

Thong

Bartels³

et al. 2014

Qual Life Res

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“…Tumor necrosis factor – alpha (TNF-α)(Aouizerat et al, 2009; Bower et al, 2013; Fung et al, 2013; Jim et al, 2012), interleukin 6 (IL6)(Inagaki et al, 2013; Rohleder et al, 2012; Schrepf et al, 2013; Schubert et al, 2007; Starkweather, 2013), and IL-1 beta (IL-1β) (Bower, 2007; Saligan and Kim, 2012; van Zuiden et al, 2012) exhibit the strongest relationships with fatigue in prior studies, although other cytokine-fatigue associations have also been reported (Bower et al, 2011; Liu et al, 2012; Piraino et al, 2012) and still other studies have yielded contradictory results (Cameron et al, 2012; Dirksen et al, 2013; Geinitz et al, 2004; Hamre et al, 2013). Both cytokine plasma concentrations and polymorphisms are implicated in fatigue, yet the nature of these relationships remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Cytokine polymorphisms are associated with fatigue in adults living with HIV/AIDS

Lee

Lerdal

Pullinger

et al. 2014

Brain, Behavior, and Immunity

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Fatigue has been associated with inflammation and cytokine activity among adults, but this relationship has not been evaluated among adults living with HIV. Diurnal patterns of fatigue have been previously identified in adults with HIV/AIDS. Thus, the purpose of this study was to describe these fatigue patterns in relation to cytokine plasma concentrations and gene polymorphisms. A convenience sample of 317 adults living with HIV/AIDS completed a measure of fatigue in the morning and evening for three consecutive days; participants reporting low levels of both morning and evening fatigue (n=110) or high levels of fatigue in the morning and evening (n=114) were included in the analysis, resulting in a final sample of 224 adults (151 men, 55 women, and 18 transgender). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB-1 and -2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. Controlling for genomic estimates of ancestry and self-reported race/ethnicity and gender, the high fatigue pattern was associated with five single nucleotide polymorphisms (SNPs): IL1B rs1071676 and rs1143627, IL4 rs2243274, and TNFA rs1800683 and rs1041981. The IL1B and TNFA polymorphisms were not associated with plasma levels of IL-1β or TNFα, respectively. This study strengthens the evidence for an association between inflammation and fatigue. In this chronic illness population, the cytokine polymorphisms associated with high levels of morning and evening fatigue provide direction for future personalized medicine intervention research.

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“…In the present study, the presence of fatigue by the VAS and severe fatigue based on the FSS-11 were both strongly associated with having a greater number of total symptoms, suggesting that fatigue is a component of what is referred to for other infectious diseases as the “acute sickness response,” which appears to be caused by the presence of pro-inflammatory cytokines and other acute phase proteins [14,15]. Prior studies in the United States of patients with erythema migrans have found evidence for increased serum levels of interferon (IFN)-gamma, interleukin-6 (IL-6), CXCL9 and/or CXCL10, depending on the particular study, in more symptomatic patients [16-18].…”

Section: Discussionmentioning

confidence: 87%

“…In certain other infections, emerging data suggest that a SNP in the IFN-gamma gene is significantly associated with experiencing severe fatigue per se [15], a topic that should be considered for potential investigation in Lyme disease patients as well.…”

Section: Discussionmentioning

confidence: 99%

Fatigue in patients with erythema migrans

Wormser

Sudhindra

Lopez

et al. 2016

Diagnostic Microbiology and Infectious Disease

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Background Fatigue is a common symptom in patients with Lyme disease. Objective The purpose of this study was to characterize fatigue in untreated adult patients presenting with erythema migrans. Selected variables were assessed to determine if any correlated with the presence or severity of fatigue. Methods Fatigue was assessed on the day of the evaluation by a visual analogue scale (VAS), over the past 14 days by the 11-item fatigue severity scale (FSS-11) and over the past 28 days based on a question from the 36-item Short Form General Health Survey version 2. Results 51 patients with erythema migrans whose mean age was 49.8 years, and 33 (64.7%) of whom were male, were evaluated in this study. The three measures of fatigue were positively correlated with one another (p ≤ 0.01). 26 (51%) had fatigue based on a VAS score above 0. 10 (19.6%) had severe fatigue based on an FSS-11 score of ≥ 4. The strongest correlate for higher fatigue scores was having a greater number of symptoms in addition to fatigue. Conclusion Based on the FSS-11 assessment tool, approximately 20% of early Lyme patients have severe fatigue. Having a high total number of symptoms was associated with both the presence and severity of fatigue. Since prior studies have demonstrated the presence of elevated levels of pro-inflammatory cytokines and other molecules in the serum of highly symptomatic patients with erythema migrans, the symptom of fatigue in early Lyme disease may be a component of what has been referred to as the acute sickness response.

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Genetic associations of fatigue and other symptom domains of the acute sickness response to infection

Cited by 59 publications

References 40 publications

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

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

Cytokine polymorphisms are associated with fatigue in adults living with HIV/AIDS

Fatigue in patients with erythema migrans

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