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  • Title: Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5).
    Author: Zampetti S, Spoletini M, Petrone A, Capizzi M, Arpi ML, Tiberti C, Di Pietro S, Bosi E, Pozzilli P, Giorgino F, Buzzetti R, Nirad Study Group.
    Journal: Diabet Med; 2010 Jun; 27(6):701-4. PubMed ID: 20546291.
    Abstract:
    AIMS: 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 (TCF7L2) 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 TCF7L2 polymorphisms. METHODS: Two hundred and fifty patients identified as LADA, divided into two subgroups with low (< or = 32 arbitrary units) or high (> 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 TCF7L2 gene using Taqman. RESULTS: 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 (P < or = 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 (P < 0.02 for all comparisons). CONCLUSIONS: TCF7L2 common genetic variants of susceptibility are associated only with low GADA antibody titre in LADA patients.
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