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Genetic association...
Genetic associations to germinal centre formation in primary Sjögren's syndrome
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- Reksten, Tove Ragna (author)
- Uppsala universitet,Reumatologi,University of Bergen, Norway / Uppsala University, Sweden
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- Johnsen, Svein Joar Auglænd (author)
- Stavanger University Hospital, Norway
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- Jonsson, Malin Viktoria (author)
- University of Bergen, Norway
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- Omdal, Roald (author)
- Stavanger University Hospital, Norway
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- Brun, Johan G (author)
- University of Bergen, Norway
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- Theander, Elke (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital, Lund University, Malmö, Sweden
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- Eriksson, Per (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet,Reumatologiska kliniken i Östergötland
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- Wahren-Herlenius, Marie (author)
- Karolinska Institutet
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- Jonsson, Roland (author)
- University of Bergen, Norway / Haukeland University Hospital, Bergen, Norway
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- Nordmark, Gunnel (author)
- Uppsala universitet,Reumatologi,Uppsala University, Sweden
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(creator_code:org_t)
- 2013-04-20
- 2014
- English.
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:6, s. 1253-1258
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Abstract
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- BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune rheumatic disease mainly characterised by focal mononuclear cell infiltration in the salivary and lacrimal glands, and by the symptoms xerostomia and keratoconjunctivitis sicca. Germinal centre-like structures (GC) are found in the minor salivary glands of approximately 25% of patients. In this study, we aimed to assess genetic variations in pSS patients with GC-like formations (GC+) compared with patients without such formations (GC−).MethodsMinor salivary gland biopsies from Swedish and Norwegian pSS patients (n=320) were evaluated for GC-like formations, identifying 76 GC+ and 244 GC− patients. A panel of 1536 single-nucleotide polymorphisms (SNPs) in 107 genes was genotyped. Minor allele frequencies in GC+ and GC− patients were compared using Fisher's exact test, and associations were considered significant when p<4.7×10−4 and suggestive when p<0.01.ResultsIn this case-only analysis, we identified two SNPs in CCL11 (eotaxin) associated with GC-like structures (p<4.7×10−4, OR 0.45 and 0.41, respectively). A haplotype of the two minor alleles was associated with GC status with p=2.6×10−4, OR 0.40. Suggestive associations (p<0.01) were found in SNPs in the B cell activation and/or GC-formation related genes AICDA, BANK1 and BCL2. Furthermore, SNPs in IL17A, ICA1, PKN1 and SNPs in the NF-κB pathway genes CARD8, IKBKE and TANK were found suggestively associated with GC-like structures.ConclusionsOur findings suggest that genetic variations may explain why ectopic GC-like structures are present in some pSS patients, and support the hypothesis that GC+ and GC− patients represent distinct disease phenotypes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Medicin
- Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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