Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association between Lymphotoxin Alpha Genetic Variants and Primary Sjgren's Syndrome in Scandinavian Samples.

Bolstad1,  Anne Isine, Le Hellard2,  Stephanie, Kristjansdottir4,  Gudlaug Thora, Nordmark4,  Gunnel, Vasaitis8,  Lilian, Kvarnstrom6,  Marika, Sjowall13,  Christopher

Department of Clinical Dentistry-Periodontics, University of Bergen, Bergen, Norway
Stavanger University Hospital, Stavanger, Norway
The Gade Institute, University of Bergen, Bergen, Norway
University Hospital Linköping, Sweden, Linköping, Sweden
University Hospital, Linköping, Linköping, Sweden
Department of Clinical Medicine, University of Bergen, Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, Sweden
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
Department of Medicine, Section of Rheumatology, University of Bergen, Bergen, Norway
Karolinska Institutet, Stockholm, Sweden
Malmö University Hospital, Malmö, Sweden
Section of Rheumatology, Uppsala University, Uppsala, Sweden
Stavanger University Hospital, Stavanger, Norway

Primary Sjögren`s syndrome (pSS) is an autoimmune chronic inflammatory disease characterized by lymphoid infiltrations of exocrine glands and increased levels of autoantibodies against the ribonucleoproteins Ro/SSA and La/SSB. Microarray studies have demonstrated increased gene expression of lymphotoxin beta (LTB) in pSS salivary glands. The aim of the present study was to investigate whether single nucleotide polymorphisms (SNPs) in the lymphotoxin alpha (LTA), LTB and tumor necrosis factor (TNF) gene clusters are associated with pSS.

A total of 527 pSS patients and 532 controls participated in the study. All of them were of Caucasian origin from Sweden and Norway. Eleven SNP markers were genotyped and analysed for their association with pSS using single marker logistic regression and for genotypic association with a chi square test. Eight markers showed significant association with pSS. The SNP rs909253 in intron 1 of LTA showed the strongest association with pSS in both the Norwegian cohort (P= 1.3E-03) and the Swedish cohort (P= 2.6E-05). Importantly, the strength of the association increased (P= 1.3E-07) when the two cohorts were analysed together, showing an odds ratio (OR) of 1.59 [95% CI: 1.34 – 1.89]. When only pSS patients positive for anti-Ro/SSA -La/SSB (n = 381) were compared with the controls, the association with SNP rs909253 was even stronger (P= 4.2E-10, OR 1.82 95% CI: 1.51–2.20). Some SNPs within this locus were also associated with extraglandular manifestations such as high plasma levels of IgG, hypothyroidism, arthritis and leucopenia in pSS patients. In conclusion, a strong association was found between several SNPs in the LTA gene locus and pSS, some of which lead to amino acid changes. Our data together with previously published reports suggest a direct role for lymphotoxin alpha in the development of pSS. The importance of this finding for the inflammatory processes in pSS needs further investigation.

To cite this abstract, please use the following information:
Bolstad, Anne Isine, Le Hellard, Stephanie, Kristjansdottir, Gudlaug Thora, Nordmark, Gunnel, Vasaitis, Lilian, Kvarnstrom, Marika, et al; Association between Lymphotoxin Alpha Genetic Variants and Primary Sjgren's Syndrome in Scandinavian Samples. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1885
DOI: 10.1002/art.29650

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