Dissecting heterogeneity in paediatric Type 1 diabetes: association of TCF7L2 rs7903146 TT and low-risk human leukocyte antigen (HLA) genotypes.
Diabet Med
; 34(2): 286-290, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-27027642
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*0301/DR4 (DRB1*0401, *0405 or *0402), compared with 29.4% (27/92) of those without it (P=0.023). The DRB1*0301 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*1501 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 1
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Diabet Med
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos