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      The clinical presentation of autoimmune thyroid disease in men is associated with IL12B genotype.

      Clinical Endocrinology
      Autoimmune Diseases, genetics, Genotype, Graves Disease, Hashimoto Disease, Humans, Interleukin-12 Subunit p40, Linkage Disequilibrium, Male, Thyroid Diseases

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          Abstract

          Common variants in the interleukin 12B (IL12B) gene are associated with predominantly inflammatory (Th1) or antibody-mediated (Th2) immune responses. As Hashimoto's disease and Graves' disease are thought to arise from mainly Th1 and Th2 immune responses respectively, we hypothesized that IL12B genotype may influence the clinical presentation of autoimmune thyroid disease. We tested for differences in IL12B genotype between Graves' disease and Hashimoto's disease. We studied a discovery cohort of 203 Australian women and 37 men with autoimmune thyroid disease, a replication cohort of 100 European men and a cohort of 146 Chinese men. We analysed three IL12B variants: rs41292470, in the promoter; rs3212227, in the 3' untranslated region and rs6887695, located 60 kilobases upstream from the coding region. In the discovery cohort, rs41292470 and rs3212227 genotypes did not differ significantly between Hashimoto's disease and Graves' disease. In Australian men (but not women), rs6887695 genotype differed between Hashimoto's disease and Graves' disease, with a minor allele frequency (MAF) of 14% and 41%, respectively (P=0·034). This result was confirmed in the European men (MAF 24% and 41%; P=0·013). On combined analysis of Australian, European and Chinese men (N=285), the difference was highly significant (MAF 23% and 45%; P=3×10(-5) ). In 233 men without thyroid disease, the MAF was 34%, significantly different from Graves' disease (P=0·005) and Hashimoto's disease (P=0·029). In men with autoimmune thyroid disease, a common variant located upstream of the IL12B coding region may influence whether patients present with Graves' disease or Hashimoto's disease. © 2011 Blackwell Publishing Ltd.

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          Author and article information

          Journal
          21198744
          10.1111/j.1365-2265.2010.03970.x

          Chemistry
          Autoimmune Diseases,genetics,Genotype,Graves Disease,Hashimoto Disease,Humans,Interleukin-12 Subunit p40,Linkage Disequilibrium,Male,Thyroid Diseases

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