Abstract
BackgroundThe protein tyrosine phosphatase N22 gene (PTPN22) encodes a lymphoid-specific phosphatase (LYP) which is an important downregulator of T cell activation. A PTPN22 polymorphism, C1858T, was found associated with type 1 diabetes (T1D) in different Caucasian populations. In this study, we aimed at confirming the role of this variant in T1D predisposition in the Spanish population.MethodsA case-control was performed with 316 Spanish white T1D patients consecutively recruited and 554 healthy controls, all of them from the Madrid area. The PTPN22 C1858T SNP was genotyped in both patients and controls using a TaqMan Assay in a 7900 HT Fast Real-Time PCR System.ResultsWe replicated for the first time in a Spanish population the association of the 1858T allele with an increased risk for developing T1D [carriers of allele T vs. CC: OR (95%) = 1.73 (1.17–2.54); p = 0.004]. Furthermore, this allele showed a significant association in female patients with diabetes onset before age 16 years [carriers of allele T vs. CC: OR (95%) = 2.95 (1.45–6.01), female patients vs female controls p = 0.0009]. No other association in specific subgroups stratified for gender, HLA susceptibility or age at onset were observed.ConclusionOur results provide evidence that the PTPN22 1858T allele is a T1D susceptibility factor also in the Spanish population and it might play a different role in susceptibility to T1D according to gender in early-onset T1D patients.
Highlights
The protein tyrosine phosphatase N22 gene (PTPN22) encodes a lymphoid-specific phosphatase (LYP) which is an important downregulator of T cell activation
Patients and controls We studied 316 white unrelated Spanish type 1 diabetes (T1D) patients (159 women and 157 men) diagnosed according to the criteria of the American Diabetes Association (ADA) and 554 healthy controls recruited among blood donors from the Madrid area
In order to study the effect of age at onset on the distribution of genotypes of this PTPN22 polymorphism, we divided our patients in two groups, setting the median age at onset in our cohort (15 years) as the cut-off value
Summary
The protein tyrosine phosphatase N22 gene (PTPN22) encodes a lymphoid-specific phosphatase (LYP) which is an important downregulator of T cell activation. BMC Medical Genetics 2007, 8:54 http://www.biomedcentral.com/1471-2350/8/54 development have been identified and were consistently replicated in independent populations [1]. These efforts contribute to a better definition of the molecular pathways leading to increased T1D risk and this knowledge, in turn, may help in understanding the genetic basis of the disease. The MHC class II, the CTLA4 and the PTPN22 loci have all been proved important in the pathogenesis of autoimmunity globally considered, whereas the insulin gene is a disease-specific T1D predisposition locus. Most of the new general susceptibility loci identified in the past few years have a clear role in the modulation of T cell development and activation, indicating that common biological pathways may be implicated in the etiology of different autoimmune diseases
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