HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holopainen, P. M. Articles by Partanen, J. A. Search for Related Content PubMed PubMed Citation Articles by Holopainen, P. M. Articles by Partanen, J. A.

Technical Note: Linkage Disequilibrium and Disease-Associated CTLA4 Gene Polymorphisms

Department of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Helsinki, Finland

Abstract

CTLA4 and CD28 are important regulators of T lymphocyte activation. Gene region 2q33 carrying genes for both CTLA4 and CD28 has been shown to be linked to many autoimmune diseases. Disease associations with particular CTLA4 gene polymorphisms have been reported. Recently, first lines of evidence emerged for functional effects of CTLA4 gene polymorphisms. Two independent studies reported a reduced inhibitory function of CTLA4 in individuals with certain CTLA4 genotypes: those with a high number of microsatellite repeats in one study and those with allele +49*G in exon 1 in the other one. We analyzed the strength of linkage disequilibrium between the three known CTLA4 polymorphisms among 577 independent chromosomes. Our results show that the polymorphisms previously suggested to be the functional risk factors nearly always occur together in a very frequent haplotype. Due to this strong linkage disequilibrium, we conclude that the previous reports studying merely a single polymorphism could not distinguish which variation actually caused the functional difference. Hence, either mutagenesis approaches or studies with data on all linked polymorphisms are still needed to determine the genuine functional risk polymorphism in this gene region.

This article has been cited by other articles:

				T.-Y. Cheng, J.-T. Lin, L.-T. Chen, C.-T. Shun, H.-P. Wang, M.-T. Lin, T.-E. Wang, A.-L. Cheng, and M.-S. Wu Association of T-Cell Regulatory Gene Polymorphisms With Susceptibility to Gastric Mucosa-Associated Lymphoid Tissue Lymphoma J. Clin. Oncol., July 20, 2006; 24(21): 3483 - 3489. [Abstract] [Full Text] [PDF]

				C G Parks, L L Hudson, G S Cooper, M A Dooley, E L Treadwell, E W St Clair, G S Gilkeson, and J P Pandey CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States Lupus, October 1, 2004; 13(10): 784 - 791. [Abstract] [PDF]

				Y. Tomer and T. F. Davies Searching for the Autoimmune Thyroid Disease Susceptibility Genes: From Gene Mapping to Gene Function Endocr. Rev., October 1, 2003; 24(5): 694 - 717. [Abstract] [Full Text] [PDF]

				B. Vaidya, P. Kendall-Taylor, and S. H. S. Pearce The Genetics of Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5385 - 5397. [Full Text] [PDF]

				S. Anjos, A. Nguyen, H. Ounissi-Benkalha, M.-C. Tessier, and C. Polychronakos A Common Autoimmunity Predisposing Signal Peptide Variant of the Cytotoxic T-lymphocyte Antigen 4 Results in Inefficient Glycosylation of the Susceptibility Allele J. Biol. Chem., November 22, 2002; 277(48): 46478 - 46486. [Abstract] [Full Text] [PDF]