Association between PTPN22 C1858T Gene Polymorphism and Graves’ Disease in Egyptians, Correlation with Tc-99m Pertechnetate Thyroid Uptake

Abstract

Background: The protein tyrosine phosphatase non receptor 22 gene (PTPN22) is an important negative regulator of signal transduction through the T-cellreceptors (TCR). A single-nucleotide polymorphism (SNP) C1858T within this gene was shown to be a risk factor for several autoimmune diseases such asGraves’disease (GD). Objective: The aim of this study was to analyze the possible association between C1858T SNP of protein tyrosine phosphatase non receptor type 22 (PTPN22) and GD in Egyptian patients and to correlate this gene expression with Tc-99m Pertechnetate uptake value and thyroid hormonal profile.Patients and Methods: The current study evaluated the PTPN22 C1858T polymorphism in 40 GD patients and 20 healthy age and sex matched control subjects with no family history of GD or any other autoimmune disease. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (RFLP).Tc-99m Pertechnetate thyroid scan and uptake was performed for GD patients. Thyroid hormonal profile including serum FT3, FT4 and TSHwas also performed for patients and control subjects.Results: No statistical significant difference in the distribution of genotypes and allelefrequency for the PTPN22 C1858T SNP between GD patients and controls (P >0.05). Genotype analysis revealed that all control group and 36/40 GD patients had the CC genotype while only 4 GD patients hadthe TT genotype. Patients with TT genotype had a significantly higher uptake % when compared with that of patients with CC genotype (26.2 ±11.5 % versus 9.2±3.1 %, respectively) (P<0.001).Conclusion: No association was found between the PTPN22 C1858Tpolymorphism and Graves’ disease in Egyptian patients. However, preliminary data suggest that the expression of TT genotype together with high Tc-99m uptake percent might be a predictor for refractory disease that would necessitate more aggressive treatment.