Association of the ACP1 genotype with metabolic parameters upon initial diagnosis of type 1 diabetes.
BACKGROUND
ACP1, also called cLMWPTP (cytosolic Low Molecular Weight PTPase) is a highly polymorphic enzyme involved in the modulation of signal transduction by insulin, PDGF receptors, and T-cell receptors. The enzyme is controlled by a locus on chromosome 2, with three common codominant alleles; the corresponding six genotypes show strong variations in total enzymatic activity. The purpose of our research was to determine the relationship of ACP1 with glycemic level, ketoacidosis and HbA1C in children with Type 1 diabetes.


METHODS
We studied 189 consecutive children with Type 1 diabetes, from the Pediatric Clinic of Sassari University. The ACP1 genotype was determined by PCR and digestion by specific restriction enzymes.


RESULTS
At initial diagnosis a strong negative correlation was observed between glycemic level and ACP1 activity, with the highest levels in genotypes with low activity. Ketoacidosis and HbA1C show a similar pattern of relationship with ACP1. A comparative analysis of the data on Type 1 diabetes with previously obtained data on Type 2 diabetes shows an opposite pattern of relationship between ACP1 and metabolic parameters. Moreover, correlation between glycemia and HbA1C in Type 1 diabetes is much weaker than in Type 2 diabetes.


CONCLUSIONS
These differences suggest that the enzyme might be involved in different signal transduction pathways relevant in the pathogenesis of these two classes of diabetic disorders. It would be interesting to study the possible correlation in Type 1 diabetes between ACP1 and immunological parameters.
Meloni
Gianfranco
G
Department of Pediatrics, University of Sassari, Italy.
Bottini
Nunzio
N
Borgiani
Paola
P
Lucarelli
Paola
P
Meloni
Tullio
T
Bottini
Egidio
E
D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D004247:DNA / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D016883:Diabetic Ketoacidosis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008297:Male; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000097:blood / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction
D001786:Blood Glucose; D004247:DNA; D006442:Glycated Hemoglobin; D007527:Isoenzymes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human