Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/24058
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Type: Journal article
Title: Influence of CTLA4 haplotypes on susceptibility and some extraglandular manifestations in primary Sjogren's syndrome
Author: Downie-Doyle, S.
Bayat, N.
Rischmueller, M.
Lester, S.
Citation: Arthritis and Rheumatism, 2006; 54(8):2434-2440
Publisher: Wiley-Liss
Issue Date: 2006
ISSN: 0004-3591
1529-0131
Statement of
Responsibility: 
Sarah Downie-Doyle, Noushin Bayat, Maureen Rischmueller and Susan Lester
Abstract: Objective Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a key negative regulator of the T cell immune response, and the CTLA4 gene is highly polymorphic. Many positive associations between CTLA4 single-nucleotide polymorphisms (SNPs) and various autoimmune diseases have been identified. Two CTLA4 SNPs that are important relative to genetic susceptibility in human autoimmune diseases are the +49GA polymorphism in exon 1 and the CT60A/G polymorphism in the 3-untranslated region. Using these 2 polymorphisms as markers, we investigated possible genetic associations of CTLA4 in Australian patients with primary Sjögren's syndrome. Methods One hundred eleven Australian Caucasian patients with primary SS and 156 population-based controls were genotyped for CTLA4 by polymerase chain reaction-restriction fragment length polymorphism methods, using the restriction enzymes BseXI (+49G/A) and HpyCh4 IV (CT60). Results The CT60 and +49G/A SNPs were in strong linkage disequilibrium, and only 3 haplotypes were observed. Significant differences in the haplotype frequencies between patients with primary SS and controls (P = 0.032) were observed, with susceptibility to primary SS associated with both the +49A;CT60A haplotype and the +49A;CT60G haplotype, whereas the +49G;CT60G haplotype was protective against primary SS. The +49A;CT60G haplotype association was predominantly with Ro/La autoantibody-positive primary SS, and the dose of this haplotype influenced the severity of daytime sleepiness (P = 0.036). The +49A;CT60A haplotype appeared to be protective against the development of Raynaud's phenomenon in patients with primary SS (odds ratio 0.49, 95% confidence interval 0.27-0.91). Conclusion The CTLA4 +49G/A and CT60 haplotypes are associated with susceptibility to primary SS and with some extraglandular manifestations of the disease.
Keywords: Humans; Sjogren's Syndrome; Disorders of Excessive Somnolence; Urologic Diseases; Genetic Predisposition to Disease; Antigens, Differentiation; Antigens, CD; Restriction Mapping; DNA Fingerprinting; Haplotypes; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Adult; Middle Aged; Female; Male; CTLA-4 Antigen
Description: Copyright © 2006, American College of Rheumatology
RMID: 0020061144
DOI: 10.1002/art.22004
Appears in Collections:Molecular and Biomedical Science publications

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