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The PTPN22 1858T gene variant in type 1 diabetes is associated with reduced residual β-cell function and worse metabolic control

¹Endocrinology, Department of Clinical Science, University "Sapienza", Polo Pontino, Rome, Italy
²Department of Public Health Sciences, University "Sapienza", Rome, Italy
³IMDIAB Group, Rome, Italy
⁴Endocrinology, University "Campus Bio-Medico", Rome, Italy
⁵Centre of Diabetes and Metabolic Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary, London, UK

raffaella.buzzetti{at}uniroma1.it

ABSTRACT

Objective: Evidence has been reported for a new susceptible locus for type 1 diabetes, the PTPN22, which encodes a lymphoid-specific phosphatase. The aim of the study was to evaluate the influence of the C1858T variant of the PTPN22 gene on b-cell function as measured by C-peptide levels from time of disease diagnosis through 12 months follow-up in a prospective series of 120 consecutive type 1 diabetes subjects.

Research Design and Methods: The C1858T polymorphism was genotyped using Taqman. Fasting C-peptide, glycated haemoglobin and insulin requirement were determined at diagnosis and every 3 months for 12 months; their change during follow up was analyzed using the general linear model repeated-measures procedure.

Results: Fasting C-peptide levels were significantly lower and HbA1c levels significantly higher in subjects carrying the PTPN22 1858T variant compared with those of subjects homozygous for C1858 from time of disease diagnosis through 12 month of intensive insulin therapy follow-up (p=0.008 and p=0.01 respectively). These findings were independent of age at onset, gender and HLA risk groups. The trend in C-peptide and HbA1c levels in the 12 month period did not differ significantly between subjects with or without the 1858T variant. Insulin dose was similar in the 1858T carriers and non-carriers.

Conclusions: Type 1 diabetes subjects carrying the 1858T variant show significant lower b-cell function and worse metabolic control at diagnosis and throughout the study period compared to subjects homozygous for C1858; these differences remain unchanged in the course of the first year after diagnosis.

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