title: A possible genetic association with chronic fatigue in primary Sjögren's syndrome: a candidate gene study.
abstract: Fatigue is prevalent and disabling in primary Sjögren's syndrome (pSS). Results from studies in chronic fatigue syndrome (CFS) indicate that genetic variation may influence fatigue. The aim of this study was to investigate single nucleotide polymorphism (SNP) variations in pSS patients with high and low fatigue. A panel of 85 SNPs in 12 genes was selected based on previous studies in CFS. A total of 207 pSS patients and 376 healthy controls were genotyped. One-hundred and ninety-three patients and 70 SNPs in 11 genes were available for analysis after quality control. Patients were dichotomized based on fatigue visual analogue scale (VAS) scores, with VAS <50 denominated "low fatigue" (n = 53) and VAS ≥50 denominated "high fatigue" (n = 140). We detected signals of association with pSS for one SNP in SLC25A40 (unadjusted p = 0.007) and two SNPs in PKN1 (both p = 0.03) in our pSS case versus control analysis. The association with SLC25A40 was stronger when only pSS high fatigue patients were analysed versus controls (p = 0.002). One SNP in PKN1 displayed an association in the case-only analysis of pSS high fatigue versus pSS low fatigue (p = 0.005). This candidate gene study in pSS did reveal a trend for associations between genetic variation in candidate genes and fatigue. The results will need to be replicated. More research on genetic associations with fatigue is warranted, and future trials should include larger cohorts and multicentre collaborations with sharing of genetic material to increase the statistical power.
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Pb. 8100 Forus, 4068, Stavanger, Norway, katnorheim@gmail.com.
authors.forename: Katrine Brække
authors.initials: KB
authors.lastname: Norheim
authors.forename: Stephanie
authors.initials: S
authors.lastname: Le Hellard
authors.forename: Gunnel
authors.initials: G
authors.lastname: Nordmark
authors.forename: Erna
authors.initials: E
authors.lastname: Harboe
authors.forename: Lasse
authors.initials: L
authors.lastname: Gøransson
authors.forename: Johan G
authors.initials: JG
authors.lastname: Brun
authors.forename: Marie
authors.initials: M
authors.lastname: Wahren-Herlenius
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
authors.forename: Roald
authors.initials: R
authors.lastname: Omdal
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D005221:Fatigue / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D009664:Norway; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011493:Protein Kinase C / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C586298:SLC25A40 protein, human; C061570:protein kinase N; D011493:Protein Kinase C