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


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 beta-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.
Petrone
Antonio
A
Endocrinology, Department of Clinical Science, University Sapienza, Polo Pontino, Rome, Italy.
Spoletini
Marialuisa
M
Zampetti
Simona
S
Capizzi
Marco
M
Zavarella
Sara
S
Osborn
John
J
Pozzilli
Paolo
P
Buzzetti
Raffaella
R
D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000502:physiology*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
D002096:C-Peptide; D017931:DNA Primers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C516765:PTPN22 protein, human