title: A systematic review of the association between fatigue and genetic polymorphisms.
abstract: Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes. To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue. SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue. We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC, United States; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, United States.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, United States; Kaiser Permanente Northern California, Division of Research, Oakland, CA, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, United States.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
authors.affiliation: School of Nursing, Emory University, Atlanta, GA, United States. Electronic address: canhua.xiao@emory.edu.
authors.forename: Canhua
authors.initials: C
authors.lastname: Xiao
mesh_terms: D005221:Fatigue / Q000209:etiology / Q000235:genetics*; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
keywords: Cancer-related fatigue; Chronic fatigue syndrome; Fatigue; Inflammation; Neurotransmitter; Single nucleotide polymorphisms