Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease.

Abstract

Our previous studies using microsatellite markers near or in the TSH receptor (TSHR) gene revealed significant association between autoimmune thyroid disease (AITD) in Japanese patients and TSHR microsatellite alleles. In the present study, we performed a case-control analysis of AITD using single-nucleotide polymorphisms (SNPs) spaced 3-50 kb apart spanning the TSHR gene. We observed significant associations between AITD/Graves' disease (GD)/Hashimoto's thyroiditis and multiple SNPs. Specifically, the SNP JST022302 and several adjacent SNPs in intron 7 of the TSHR gene were significantly associated with GD (P = 0.039-0.0004) but not Hashimoto's thyroiditis. Furthermore, we identified three haplotype blocks around intron 7 by linkage disequilibrium analysis. A single SNP haplotype [AATG(CT)6(TT)AG] in the haplotype block including JST022302 showed significant association with GD in haplotype case-control analysis (P = 0.0058). These findings suggest that alleles of intron 7 of the TSHR gene contribute to GD susceptibility.

• Authors: Hitomi Hiratani, Donald W Bowden, Satoshi Ikegami, Senji Shirasawa, Akira Shimizu, Yoshinori Iwatani, Takashi Akamizu
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 90 Issue 5 Pg. 2898-903 (May 2005) ISSN: 0021-972X [Print] United States
• PMID: 15741259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Thyrotropin

Topics

• Case-Control Studies
• Female
• Gene Frequency
• Graves Disease (genetics)
• Haplotypes
• Humans
• Introns
• Linkage Disequilibrium
• Male
• Polymorphism, Single Nucleotide
• Receptors, Thyrotropin (genetics)