Eastern Regional Meeting - 2008 Program & Abstracts
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Association of a Common Variant of the Signal Transducer and Activator of Transcription 4 (STAT4) Gene with Primary Sjögren’s Syndrome
B.D. Korman, J. Le, D. Kastner, E. Remmers, Genetics and Genomics Branch, National Institute of Arthritis Muskuloskeletal and Skin Diseases, Bethesda, MD; M. Alba, I. Alevizos, N. Nikolov, G. Illei, Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, Bethesda, MD; M. Alba, I. Alevizos, N. Nikolov, G. Illei, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD; J. Smith, Office of the Clinical Director, National Eye Institute , Bethesda, MD; B.D. Korman, Clinical Research Training Program, National Institutes of Health, Bethesda, MD
Purpose of Study: A haplotype of an LD block located within the third large intron of the STAT4 gene was recently shown to be a risk factor for both rheumatoid arthritis and systemic lupus erythematosus. We sought to determine whether this variant is associated with a related but mutually exclusive autoimmune disease, primary Sjögren’s syndrome.
Methods Used: Caucasian patients with definite primary Sjögren’s syndrome (n = 124) as identified by the American-European Revised Consensus Criteria at the Sjögren’s clinic of the National Institute of Dental and Craniofacial Research were genotyped for rs7574865 using the HME multi-base primer extension method (Sequenom, San Diego, California, USA). Control genotypes (n = 1143) were obtained from healthy Caucasian smokers previously genotyped with the Illumina Infinium II HumanHap300 SNP chip (Illumina, San Diego) as part of the MD Anderson bronchogenic carcinoma study. Disease association was evaluated with a chi squared test comparing allele frequency in cases with controls.
Summary of Results: The rs7574865 disease-associated T allele was more common in the chromosomes of primary Sjögren’s syndrome patients (29.6%) versus controls (22.3%) leading to a p-value for association of 0.01.
Conclusions: These results implicate STAT4 in the pathogenesis of primary Sjögren’s syndrome. Although Sjögren’s syndrome is frequently found secondary to other autoimmune diseases, primary Sjögren’s syndrome excludes these cases and is therefore a distinct autoimmune disease. Taken together with the previously identified associations in RA and SLE, this study suggests that the common STAT4 variant tagged by the rs7574865 minor allele may be a generalized contributor to autoimmune disease.
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