The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.

Abstract

BACKGROUND:

The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene was recently associated with autoimmune thyroid disease (AITD) and type I diabetes (T1D). The purpose of this study was to examine the joint association of this polymorphism with the co-occurrence of AITD and T1D.

METHODS:

In this association study, 310 white subjects were genotyped for the C1858T polymorphism. The study population included 70 patients with both AITD and T1D (AITD+T1D), 70 patients with AITD only, 70 patients with T1D only, and 100 healthy controls. Patients with both AITD and T1D, and controls were also typed for HLA-DRB1. PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing, polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were used.

RESULTS:

The PTPN22 1858 minor T-allele frequency was strongly increased in patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T-allele carriers were also more frequently present in the group with AITD+T1D versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%, OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45). Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001). Considering all included patients with AITD, T-allele carriers were 29.3% vs. 14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele (64.7% vs. 37.3%, pc=0.034).

CONCLUSION:

The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.

• Authors: Georg Dultz, Nina Matheis, Manuela Dittmar, Bernd Röhrig, Klaus Bender, George J Kahaly
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 19 Issue 2 Pg. 143-8 (Feb 2009) ISSN: 1557-9077 [Electronic] United States
• PMID: 19090780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• PTPN22 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 22

Topics

• Adolescent
• Adult
• Amino Acid Sequence
• Autoantibodies
• Base Sequence
• Child
• Diabetes Mellitus, Type 1 (complications, genetics)
• Genetic Predisposition to Disease
• Humans
• Middle Aged
• Molecular Sequence Data
• Point Mutation
• Polymorphism, Single Nucleotide
• Protein Tyrosine Phosphatase, Non-Receptor Type 22 (genetics)
• Thyroid Gland (immunology)
• Thyroiditis, Autoimmune (complications, genetics)