Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015674 (chronic fatigue syndrome)
 2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown etiology with no known lesions, diagnostic markers or therapeutic intervention. The pathophysiology of CFS remains elusive, although abnormalities in the central nervous system (CNS) have been implicated, particularly hyperactivity of the serotonergic (5-hydroxytryptamine; 5-HT) system and hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since alterations in 5-HT signaling can lead to physiologic and behavioral changes, a genetic evaluation of the 5-HT system was undertaken to identify serotonergic markers associated with CFS and potential mechanisms for CNS abnormality. A total of 77 polymorphisms in genes related to serotonin synthesis (TPH2), signaling (HTR1A, HTR1E, HTR2A, HTR2B, HTR2C, HTR3A, HTR3B, HTR4, HTR5A, HTR6, and HTR7), transport (SLC6A4), and catabolism (MAOA) were examined in 137 clinically evaluated subjects (40 CFS, 55 with insufficient fatigue, and 42 non-fatigued, NF, controls) derived from a population-based CFS surveillance study in Wichita, Kansas. Of the polymorphisms examined, three markers (-1438G/A, C102T, and rs1923884) all located in the 5-HT receptor subtype HTR2A were associated with CFS when compared to NF controls. Additionally, consistent associations were observed between HTR2A variants and quantitative measures of disability and fatigue in all subjects. The most compelling of these associations was with the A allele of -1438G/A (rs6311) which is suggested to have increased promoter activity in functional studies. Further, in silico analysis revealed that the -1438 A allele creates a consensus binding site for Th1/E47, a transcription factor implicated in the development of the nervous system. Electrophoretic mobility shift assay supports allele-specific binding of E47 to the A allele but not the G allele at this locus. These data indicate that sequence variation in HTR2A, potentially resulting in its enhanced activity, may be involved in the pathophysiology of CFS.
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PMID:Genetic evaluation of the serotonergic system in chronic fatigue syndrome. 1807 67

Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI). Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.
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PMID:Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype. 2647 96