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Zampetti, S.; Spoletini, M.; Petrone, A.; Capizzi, M.; Arpi, M. L.; Tiberti, C.; Di Pietro, S.; Bosi, E.; Pozzilli, P.; Giorgino, F.; Buzzetti for the NIRAD Study Group, R.

Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5)

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  • Medientyp: E-Artikel
  • Titel: Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5)
  • Beteiligte: Zampetti, S.; Spoletini, M.; Petrone, A.; Capizzi, M.; Arpi, M. L.; Tiberti, C.; Di Pietro, S.; Bosi, E.; Pozzilli, P.; Giorgino, F.; Buzzetti for the NIRAD Study Group, R.
  • Erschienen: Wiley, 2010
  • Erschienen in: Diabetic Medicine
  • Sprache: Englisch
  • DOI: 10.1111/j.1464-5491.2010.02997.x
  • ISSN: 0742-3071; 1464-5491
  • Schlagwörter: Endocrinology ; Endocrinology, Diabetes and Metabolism ; Internal Medicine
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  • Beschreibung: <jats:sec><jats:label /><jats:p>Diabet. Med. 27, 701–704 (2010)</jats:p></jats:sec><jats:sec><jats:title>Abstract</jats:title><jats:p><jats:bold>Aims </jats:bold> We previously demonstrated the presence of two different populations among adult‐onset autoimmune diabetes (latent autoimmume diabetes of adults; LADA) having high or low titre of antibodies to glutamic acid decarboxylase (GADA). The transcription factor 7‐like 2 (<jats:italic>TCF7L2</jats:italic>) gene has been recognized as the major gene associated with Type 2 diabetes. The aim of the present study was to evaluate whether the phenotypic heterogeneity of LADA based on GADA titre is associated with <jats:italic>TCF7L2</jats:italic> polymorphisms.</jats:p><jats:p><jats:bold>Methods </jats:bold> Two hundred and fifty patients identified as LADA, divided into two subgroups with low (≤ 32 arbitrary units) or high (&gt; 32 units) GADA titre, 620 subjects with Type 2 diabetes [from the Non‐Insulin Requiring Autoimmune Diabetes (NIRAD) study cohort of 5330 subjects] in addition to 551 consecutive cases of Type 1 diabetes and 545 normoglycaemic subjects were analysed for the rs12255372 and rs7903146 polymorphisms of the <jats:italic>TCF7L2</jats:italic> gene using Taqman.</jats:p><jats:p><jats:bold>Results </jats:bold> The genotype and allele distributions of the two polymorphisms revealed similar frequencies in subjects with low GADA titre and Type 2 diabetes. High GADA titre, Type 1 diabetes and controls also showed comparable frequencies. A significant increase of GT/TT genotypes of the rs12255372 single‐nucleotide polymorphism (SNP) and CT/TT genotypes of the rs7903146 SNP was observed in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and controls (<jats:italic>P</jats:italic> ≤ 0.04 for both comparisons). The risk alleles of both variants were increased in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and control subjects (<jats:italic>P</jats:italic> &lt; 0.02 for all comparisons).</jats:p><jats:p><jats:bold>Conclusions </jats:bold> <jats:italic>TCF7L2</jats:italic> common genetic variants of susceptibility are associated only with low GADA antibody titre in LADA patients.</jats:p></jats:sec>