title: Genes that characterize T3-predominant Graves' thyroid tissues.
abstract: OBJECTIVE
  3,5,3'-Triiodothyronine (T(3))-predominant Graves' disease is characterized by the increasing volume of thyroid goiter resulting in poor prognosis. Although type 1 and type 2 iodothyronine deiodinases (DIO1 and DIO2 respectively) are known to be overexpressed in the thyroid tissues of T(3)-predominant Graves' disease, the pathogenesis of this disease is still unclear. The aim of our study is to identify genes that characterize T(3)-predominant Graves' disease tissue in order to clarify the molecular mechanism of this disease.
  
  
  METHODS
  mRNAs from two thyroid tissues of both typical T(3)-predominant and common-type Graves' disease were analyzed with DNA microarrays with probes for 28 869 genes. Genes identified to be differentially expressed between the two groups were further analyzed in the second and third screenings using 70 Graves' thyroid tissues by real-time quantitative RT-PCR.
  
  
  RESULTS
  Twenty-three candidate genes were selected as being differentially expressed in the first screening with microarrays. Among these, seven genes, leucine-rich repeat neuronal 1 (LRRN1), bone morphogenetic protein 8a (BMP8A), N-cadherin (CDH2), phosphodiesterase 1A (PDE1A), creatine kinase mitochondrial 2 (CKMT2), integrin beta-3 (ITGB3), and protein tyrosine phosphatase non-receptor type 4 (PTPN4), were confirmed to be differentially expressed in DIO1 or DIO2 over- and underexpressing Graves' tissues.
  
  
  CONCLUSIONS
  These genes are related to the characteristics of T(3)-predominant Graves' disease, such as high titer level of serum anti-TSH receptor antibody, high free T(3) to free thyroxine ratio, and a large goiter size. They might play a role in the pathogenesis of T(3)-predominant Graves' disease.
authors.affiliation: Department of Laboratory Medicine, Osaka University Graduate School of Medicine, D2, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ito
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yamada
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Arisa
authors.initials: A
authors.lastname: Date
authors.forename: Mikio
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yoh
authors.initials: Y
authors.lastname: Hidaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Iwatani
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Toru
authors.initials: T
authors.lastname: Takano
mesh_terms: D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism; D052281:Creatine Kinase, Mitochondrial Form; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006111:Graves Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D054590:Protein Tyrosine Phosphatase, Non-Receptor Type 4 / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: C485773:BMP8A protein, human; D019485:Bone Morphogenetic Proteins; D015820:Cadherins; D039661:Integrin beta3; C494421:LRRN1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D014284:Triiodothyronine; D007453:Iodide Peroxidase; C521170:CKMT2 protein, human; D003402:Creatine Kinase; D052281:Creatine Kinase, Mitochondrial Form; C516658:PTPN4 protein, human; D054590:Protein Tyrosine Phosphatase, Non-Receptor Type 4; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517265:PDE1A protein, human; D013974:Thyroxine