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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

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

Corresponding author: Professor Raffaella Buzzetti, Department of Clinical Science, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. E-mail: raffaella.buzzetti{at}uniroma1.it

OBJECTIVE—Evidence has been reported for a new susceptible locus for type 1 diabetes, the protein tyrosine phosphatase nonreceptor type 2 (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 β-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 diabetic subjects.

RESEARCH DESIGN AND METHODS—The C1858T polymorphism was genotyped using TaqMan. Fasting C-peptide, A1C, and insulin requirements 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 A1C levels were significantly higher in subjects carrying the PTPN22 1858T variant than in subjects homozygous for C1858 from time of disease diagnosis through 12 months of intensive insulin therapy follow-up (P = 0.008 and P = 0.01, respectively). These findings were independent of age at onset, sex, and HLA risk groups. The trend in C-peptide and A1C 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 noncarriers.

CONCLUSIONS—Type 1 diabetic subjects carrying the 1858T variant show significantly lower β-cell function and worse metabolic control at diagnosis and throughout the study period than subjects homozygous for C1858; these differences remain unchanged over the course of the first year after diagnosis.

Abbreviations: IMDIAB, Immunotherapy Diabetes • LYP, lymphoid tyrosine phosphatase • PTPN22, protein tyrosine phosphatase nonreceptor type 2 • SNP, single nucleotide polymorphism

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