title: Association of autoimmune thyroid disease with a microsatellite marker for the thyrotropin receptor gene and CTLA-4 in a Japanese population.
abstract: To examine the genetic contribution of the thyroid-stimulating hormone receptor (TSHR, or thyrotropin receptor) gene to autoimmune thyroid disease (AITD), we identified a dinucleotide repeat polymorphism near the TSHR gene that mapped to an 8.6 cM interval between D14S74 and D14S55 on the long arm of human chromosome 14. Association studies revealed a significant difference (p = 3.8 x 10(-5) between the TSHR microsatellite allele frequency distribution in 81 unrelated Japanese AITD patients and 113 Japanese controls, with a significant increase in the 180 pb allele (allele 1) of the microsatellite sequence (p = 5.8 x 10(-7). The risk for AITD with the 180 bp allele was 3.5, with association highly significant in female patients (p = 1.1 x 10(-5) and less dramatic, but still significant, in male patients (p = .02). These results suggest that the 180 bp allele of the TSHR microsatellite is associated with a susceptibility locus for AITD in Japanese patients. Two additional genetic markers have been evaluated for association in the Japanese AITD patients. The TSHR codon 52 (C52-->A52) transition mutation was not observed in the Japanese. A polymorphism for the CTLA-4 gene was genotyped and, while association with AITD was not observed (p = .15), a significant association was observed between CTLA-4 alleles of 110 bp (p = .01) and 106 bp (p = .004) and susceptibility to primary hypothyroidism or idiopathic myxedema, respectively.
authors.affiliation: Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Sale
authors.forename: T
authors.initials: T
authors.lastname: Akamizu
authors.forename: T D
authors.initials: TD
authors.lastname: Howard
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: H
authors.initials: H
authors.lastname: Iwasaki
authors.forename: S S
authors.initials: SS
authors.lastname: Rich
authors.forename: J E
authors.initials: JE
authors.lastname: Jennings-Gee
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: D W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D006111:Graves Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics / Q000276:immunology; D018796:Immunoconjugates; D007564:Japan; D008297:Male; D009010:Monte Carlo Method; D009230:Myxedema / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D011989:Receptors, Thyrotropin / Q000235:genetics*; D012737:Sex Factors; D013959:Thyroid Diseases / Q000235:genetics* / Q000276:immunology; D013966:Thyroiditis / Q000235:genetics; D013967:Thyroiditis, Autoimmune / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D011989:Receptors, Thyrotropin; D000069594:Abatacept