NDLI: Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease.

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Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease.

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Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tomer, Yaron Ban, Yoshiyuki Greenberg, David A. Skrabanek, Lucy Villanueva, Ronald Concepcion, Erlinda
Description	Author Affiliation: Ban Y ( Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. yoshiyuki_ban@mssm.edu);
Abstract	The 8q24 locus, which contains the thyroglobulin (Tg) gene, was previously shown to be strongly linked with autoimmune thyroid disease (AITD). We sequenced all 48 exons of the Tg gene and identified 14 single-nucleotide polymorphisms (SNPs). Case control association studies demonstrated that an exon 10-12 SNP cluster and an exon 33 SNP were significantly associated with AITD (P < 0.01). Haplotype analysis demonstrated that the combination of these two SNP groups was more significantly associated with AITD (P < 0.001). Gene-gene interaction studies provided evidence for an interaction between HLA-DR3 and the exon 33 SNP, giving an odds ratio of 6.1 for Graves' disease. We then sequenced exons 10,12, and 33 of the mouse Tg gene in 19 strains of mice. Fifty percent of the strains susceptible to thyroiditis had a unique SNP haplotype at exons 10 and 12, whereas none of the mouse strains that were resistant to thyroiditis had this SNP haplotype (P = 0.01). We concluded that Tg is a susceptibility gene for AITD, both in humans in and in mice. A combination of at least two Tg SNPs conferred susceptibility to human AITD. Moreover, the exon 33 SNP showed evidence for interaction with HLA-DR3 in conferring susceptibility to Graves' disease.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	25
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Mutation Thyroglobulin Genetics Thyroiditis, Autoimmune Alleles Animals Exons Gene Deletion Genetic Predisposition To Disease Graves Disease HLA-DR3 Antigen Haplotypes Mice Mice, Inbred CBA Odds Ratio Polymorphism, Genetic Polymorphism, Single Nucleotide Sequence Analysis, DNA Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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