title: 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.affiliation: Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto University School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hiratani
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikegami
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Iwatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Akamizu
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006111:Graves Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011989:Receptors, Thyrotropin / Q000235:genetics*
chemical_list: D011989:Receptors, Thyrotropin