Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.
Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing fatigue that is not alleviated by rest, causes substantial reduction in activities and is accompanied by a variety of symptoms. Its unknown etiology may reflect that CFS is heterogeneous. Latent class analyses of symptoms and physiological systems were used to delineate subgroups within a population-based sample of fatigued and nonfatigued subjects [1] . This study examined whether genetic differences underlie the individual subgroups of the latent class solution. Polymorphisms in 11 candidate genes related to both hypothalamic-pituitary-adrenal (HPA) axis function and mood-related neurotransmitter systems were evaluated by comparing each of the five ill classes (Class 1, n = 33; Class 3, n = 22; Class 4, n = 22; Class 5, n = 17; Class 6, n = 11) of fatigued subjects with subjects defined as well (Class 2, n = 35). Of the five classes of subjects with unexplained fatigue, three classes were distinguished by gene polymorphsims involved in either HPA axis function or neurotransmitter systems, including proopiomelanocortin (POMC), nuclear receptor subfamily 3, group C, member 1 (NR3C1), monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and tryptophan hydroxylase 2 (TPH2). These data support the hypothesis that medically unexplained chronic fatigue is heterogeneous and presents preliminary evidence of the genetic mechanisms underlying some of the putative conditions.
Smith
Alicia K
AK
Centers for Disease Control and Prevention, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, 1600 Clifton Road, MSG41, Atlanta, GA 30333, USA.
White
Peter D
PD
Aslakson
Eric
E
Vollmer-Conna
Ute
U
Rajeevan
Mangalathu S
MS
D000339:Affect / Q000502:physiology; D000483:Alleles; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D015673:Fatigue Syndrome, Chronic / Q000145:classification* / Q000235:genetics* / Q000503:physiopathology; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000502:physiology; D010907:Pituitary Hormones / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics
D018377:Neurotransmitter Agents; D010907:Pituitary Hormones; D004247:DNA