Journal
THYROID
Volume 19, Issue 2, Pages 143-148Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/thy.2008.0301
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Funding
- Gutenberg University (Maifor)
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Background: The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase nonreceptor 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 cooccurrence 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%, p(c) < 0.001), with patients with AITD only (8.6%, p(c) = 0.006), or with T1D only (10.7%, p(c) = 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, p(c) < 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%, p(c) = 0.034). Conclusion: The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.
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