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A possible genetic association with chronic fatigue in primary Sjögren’s syndrome: a candidate gene study

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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.

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Acknowledgments

We thank Per Lundmark for selecting tag-SNPs. This work was supported by an internal research grant from Stavanger University Hospital to KBN, Grant number N/A.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Pb. 8100 Forus, 4068, Stavanger, Norway

    Katrine Brække Norheim, Erna Harboe, Lasse Gøransson & Roald Omdal

  2. Department of Clinical Medicine, Dr E. Martens Research Group for Biological Psychiatry, University of Bergen, Bergen, Norway

    Stephanie Le Hellard

  3. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    Stephanie Le Hellard

  4. Section of Rheumatology¸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    Gunnel Nordmark

  5. Institute of Medicine, University of Bergen, Bergen, Norway

    Lasse Gøransson, Johan G. Brun, Roland Jonsson & Roald Omdal

  6. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway

    Johan G. Brun

  7. Rheumatology Unit, Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

    Marie Wahren-Herlenius

  8. Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway

    Roland Jonsson

Authors
  1. Katrine Brække Norheim
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  2. Stephanie Le Hellard
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Correspondence to Katrine Brække Norheim.

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Norheim, K.B., Le Hellard, S., Nordmark, G. et al. A possible genetic association with chronic fatigue in primary Sjögren’s syndrome: a candidate gene study. Rheumatol Int 34, 191–197 (2014). https://doi.org/10.1007/s00296-013-2850-9

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  • DOI: https://doi.org/10.1007/s00296-013-2850-9

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