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Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Association of autoimmune thyroid disease with a microsatellite marker for the thyrotropin receptor gene and CTLA-4 in a Japanese population.
Proceedings of the Association of American Physicians 1997 September
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.
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