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Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts.
Mitchell, Anna L; Macarthur, Katie D R; Gan, Earn H; Baggott, Lucy E; Wolff, Anette S B; Skinningsrud, Beate; Platt, Hazel; Short, Andrea; Lobell, Anna; Kämpe, Olle; Bensing, Sophie; Betterle, Corrado; Kasperlik-Zaluska, Anna; Zurawek, Magdalena; Fichna, Marta; Kockum, Ingrid; Nordling Eriksson, Gabriel; Ekwall, Olov; Wahlberg, Jeanette; Dahlqvist, Per; Hulting, Anna-Lena; Penna-Martinez, Marissa; Meyer, Gesine; Kahles, Heinrich; Badenhoop, Klaus; Hahner, Stephanie; Quinkler, Marcus; Falorni, Alberto; Phipps-Green, Amanda; Merriman, Tony R; Ollier, William; Cordell, Heather J; Undlien, Dag; Czarnocka, Barbara; Husebye, Eystein; Pearce, Simon H S.
Afiliação
  • Mitchell AL; Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
  • Macarthur KD; Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
  • Gan EH; Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
  • Baggott LE; Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
  • Wolff AS; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Skinningsrud B; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway.
  • Platt H; CIGMR, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
  • Short A; CIGMR, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
  • Lobell A; Uppsala University, Uppsala, Sweden.
  • Kämpe O; Uppsala University, Uppsala, Sweden.
  • Bensing S; Uppsala University, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden.
  • Betterle C; Department of Medicine, University of Padua School of Medicine, Padua, Italy.
  • Kasperlik-Zaluska A; Department of Endocrinology, Center for Postgraduate Medical Education, Warsaw, Poland.
  • Zurawek M; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
  • Fichna M; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
  • Kockum I; Neuroimmunology Unit, Department of Clinical Neuroscience and Centrum for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Nordling Eriksson G; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Ekwall O; The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Wahlberg J; Department of Medical and Health Sciences, Division of Endocrinology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
  • Dahlqvist P; Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
  • Hulting AL; Karolinska Institutet, Stockholm, Sweden.
  • Penna-Martinez M; Department Medicine (Division Endocrinology), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
  • Meyer G; Department Medicine (Division Endocrinology), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
  • Kahles H; Department Medicine (Division Endocrinology), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
  • Badenhoop K; Department Medicine (Division Endocrinology), University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
  • Hahner S; University Hospital Wuerzburg (Department of Medicine, Endocrinology and Diabetology), Wuerzburg, Germany.
  • Quinkler M; Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany.
  • Falorni A; Department of Internal Medicine, University of Perugia, Perugia, Italy.
  • Phipps-Green A; Department of Biochemistry, University of Otago, Otago, New Zealand.
  • Merriman TR; Department of Biochemistry, University of Otago, Otago, New Zealand.
  • Ollier W; CIGMR, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
  • Cordell HJ; Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
  • Undlien D; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway.
  • Czarnocka B; Department of Biochemistry and Molecular Biology, Center for Postgraduate Medical Education, Warsaw, Poland.
  • Husebye E; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway.
  • Pearce SH; Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
PLoS One ; 9(3): e88991, 2014.
Article em En | MEDLINE | ID: mdl-24614117
ABSTRACT

BACKGROUND:

Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.

AIM:

To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.

METHODS:

A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.

RESULTS:

We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624 P = 0.00016; rs10931481 P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.

CONCLUSIONS:

Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Autoimunes / Doença de Addison / Predisposição Genética para Doença / Alelos / Fator de Transcrição STAT4 / Fator de Transcrição GATA3 / Estudos de Associação Genética Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Infant / Male País/Região como assunto: Europa Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Autoimunes / Doença de Addison / Predisposição Genética para Doença / Alelos / Fator de Transcrição STAT4 / Fator de Transcrição GATA3 / Estudos de Associação Genética Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Infant / Male País/Região como assunto: Europa Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido