Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases

Yaron Tomer, David A. Greenberg, Erlinda Concepcion, Yoshiyuki Ban, Terry F. Davies

Research output: Contribution to journalArticle

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Abstract

The autoimmune thyroid diseases (AITDs) develop as a result of a complex interaction between predisposing genes and non-genetic factors. We have completed a whole genome scan in 56 families which revealed 7 major AITD loci (LOD scores >2), and additional minor loci (LOD scores > 1). One of the minor loci was on chromosome 8q24 giving a maximum LOD score (MLS) of 1.8 at marker D8S284. This locus contained the thyroglobulin (Tg) gene which was a strong candidate gene for AITD. Because of this we analyzed the Tg gene region in detail using an expanded dataset of 102 families. The new linkage analysis showed stronger evidence for linkage at the Tg gene locus with an MLS of 3.5 between markers D8S514 and D8S284 (NPL=2.0). We then proceeded to analyze the Tg gene directly. We identified a new microsatellite inside intron 27 of the Tg gene (designated Tgms2). Tgms2 showed strong evidence for linkage with AITD (MLS=2.9), further suggesting that the Tg gene was linked to AITD. Association studies comparing 224 Caucasian AITD patients to 134 Caucasian controls showed an association of Tgms2 with AITD (p=0.05, relative risk [RR]= 1.4).The association was stronger when only the probands from the linked families (n=32) were used (p=0.004, RR=2.3). Transmission disequilibrium test (TDT) analysis also showed an association of Tgms2 with AITD (p=0.02). We concluded therefore that the Tg gene was a major AITD susceptibility gene because it was both linked and associated with AITD.

Original languageEnglish (US)
Pages (from-to)404-407
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Thyroglobulin
Thyroid Diseases
Autoimmune Diseases
Thyroid Gland
Genes
Disease Susceptibility
Chromosomes
Microsatellite Repeats
Introns
Genome

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases. / Tomer, Yaron; Greenberg, David A.; Concepcion, Erlinda; Ban, Yoshiyuki; Davies, Terry F.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 1, 2002, p. 404-407.

Research output: Contribution to journalArticle

Tomer, Yaron ; Greenberg, David A. ; Concepcion, Erlinda ; Ban, Yoshiyuki ; Davies, Terry F. / Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 1. pp. 404-407.
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