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This version published online on June 17, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0364
A more recent version of this article appeared on September 1, 2008
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Right arrow Thyroid
Right arrow Autoimmunity

Submitted on February 14, 2008
Accepted on June 5, 2008

LINKAGE ANALYSIS OF THYROID ANTIBODY PRODUCTION: EVIDENCE FOR SHARED SUSCEPTIBILITY TO CLINICAL AUTOIMMUNE THYROID DISEASE

Yoshiyuki Ban, David A. Greenberg, Terry F. Davies, Eric Jacobson, Erlinda Concepcion, and Yaron Tomer*

Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan; Division of Statistical Genetics, Columbia University, New York, NY, USA; Division of Endocrinology, James J. Peters VA Medical Center, Mount Sinai School of Medicine, New York, NY, USA; Division of Endocrinology, University of Cincinnati College of Medicine, and Cincinnati VA Medical Center, Cincinnati, OH, USA

* To whom correspondence should be addressed. E-mail: Yaron.Tomer{at}UC.edu.

Context: Epidemiological data suggest a genetic susceptibility to thyroid antibody (TAb) production.

Objective: To identify genetic loci which are linked with TAb production.

Design: A whole genome linkage study in families with clustering of thyroid autoimmunity.

Settings: The study took place at an academic medical center.

Participants: Participants included 102 multi-generational families (540 individuals) multiplex for autoimmune thyroid disease (AITD), and TAb production.

Main Outcome Measures: We computed 2-point logarithm of odds (LOD) scores and multipoint heterogeneity LOD scores for 400 microsatellite markers spanning the entire human genome at an average distance of 10 cM (~10 Mb).

Results: Three loci showed evidence for linkage with TAb production: (1) 2q locus - gave a maximum multipoint heterogeneity LOD score (HLOD) of 2.8 and contained the CTLA-4 gene, previously reported to be linked and associated with clinical AITD; (2) 6p locus (HLOD 2.5) - was the same AITD-1 locus found to be linked with clinical AITD; (3) 8q locus (HLOD 2.2) - contained the thyroglobulin (Tg) gene, also previously reported to be linked and associated with AITD. All loci that were linked to TAb were also linked to AITD, suggesting that TAb and AITD share the same genetic predisposition.

Conclusions: We conclude that: (1) Some of the genes/loci predisposing to TAb and AITD are shared, while distinct genes/loci also exist; (2) The presence of TAb in relatives of AITD patients may be associated with increased risk for the development of clinical AITD; (3) Further studies are needed to determine the predictive value of TAb levels for the development of clinical AITD in relatives of patients with familial AITD.
Key words: Thyroid • Autoantibodies • Genes • Linkage • Autoimmunity






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