Dissecting heterogeneity in paediatric Type 1 diabetes: association of : M. J. Redondo et al.TCF7L2: M. J. Redondo et al. rs7903146 TT and low-risk human leukocyte antigen (HLA) genotypes: M. J. Redondo et al.

    loading  Checking for direct PDF access through Ovid

Abstract

Aims

To test the hypothesis that non-obese individuals with childhood-onset Type 1 diabetes and the rs7903146 TT genotype would be less likely to have high-risk human leukocyte antigen (HLA) genotypes and alleles.

Methods

We studied a cohort of 105 non-obese participants in the T1D Exchange Biobank Residual Insulin Study who had childhood-onset Type 1 diabetes [mean (sd) age at onset and recruitment, respectively, 9.9 (4.15) and 14.4 (4.13) years; 84.8% non-Hispanic white]. We analysed islet autoantibodies (glutamic acid decarboxylase 65, islet cell autoantigen 512/islet antigen-2 and zinc transporter 8), non-fasting random C-peptide levels, HLA type and TCF7L2 single nucleotide polymorphism rs7903146 in this cohort.

Results

None of the 13 individuals with the rs7903146 TT genotype carried the highest Type 1 diabetes risk HLA genotype, i.e. DRB1*03:01/DR4 (DRB1*0401, *04:05 or *04:02), compared with 29.4% (27/92) of those without it (P=0.023). The DRB1*03:01 allele was present in 15.4% (2/13) of individuals with the single nucleotide polymorphism, compared with 59.8% (55/92) of those without it (P=0.003). Analyses restricted to autoantibody-positive individuals (n=80) yielded similar results. The HLA DRB1*15:01 allele, which affords dominant protection against Type 1 diabetes, was found in one participant, who had multiple islet autoantibodies and carried the rs7903146 TT genotype.

Conclusions

These findings further support the hypothesis that TCF7L2 gene variation contributes to diabetogenesis in a subset of young people with Type 1 diabetes, opening possible new pathways for therapy and prevention.

Related Topics

    loading  Loading Related Articles