PTPN22 gene and IL2RA rs11594656, rs2104286 gene variants: additional insights of polygenic single-nucleotide polymorphisms’ pattern among Egyptian children with type 1 diabetes

Background Type 1 diabetes mellitus (T1D) results from environmental and genetic factors. We aimed to investigate the distribution of PTPN22, IL2RA rs11594656, and rs2104286 variants and its association with T1D in children. A case-control study conducted on 100 diabetic patients and 100 control children. PTPN22 gene, IL2RA rs11594656, and rs2104286 polymorphisms study were done by PCR followed by restriction fragment length polymorphism (RFLP) assay. Results T allele of PTPN22 gene was presented more frequently 47% in patient group versus 30% in controls, while C allele was 53% in the diabetic group versus 70% in controls showing a statistically significant difference between patient and control groups. Similarly, TT 1858 genotype was found in higher frequency with a statistically significant difference in favor of T1D patients (p = 0.038), OR (CI 95% 3.16 (1.28–7.09). For IL2RA rs11594656 polymorphism, the frequency of TT, TA, and AA in patients at percentages of 20%, 60%, and 20% versus 4%, 60%, and 36% in controls respectively showed significant difference (p = 0.045). Also, T allele was detected more in patients group as evidenced by p = 0.059, OR (95% CI) of 2.38(1.49–6.12). Whereas, IL2RA rs2104286 polymorphism revealed a difference of otherwise non-statistical significance (p = 0.091). Those who harbored homozygous pattern of both IL2RA polymorphisms frequently had DKA and high mean HbA1C values. Conclusion PTPN22 (C1858T) and IL2RA rs11594656 polymorphisms increased the risk of T1DM development, while IL2RA rs2104286 polymorphism did not display any significant association among children with T1D. Having more than one risk allele could affect progression and control of T1D.

Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with unexplained recurrent pregnancy loss: A case-control study

Background: Lymphoid-tyrosine-phosphatase which is encoded by the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays a pivotal role in the regulation of immune responses by dephosphorylating several signaling intermediates of immune cells. Objective: Since a balanced immune response has been shown to be important during pregnancy, the purpose of this research was to compare the frequency of the PTPN22 C1858T polymorphism in women with unexplained recurrent pregnancy loss (URPL) vs. in a control group for the first time. Materials and Methods: Genomic DNA from 200 individuals with URPL and 200 individuals without URPL (the control group) at the infertility center in Yazd, Iran was isolated using the salting-out method. The PTPN22 C1858T polymorphism of the two groups was analyzed using polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies in the women with URPL and the fertile control group were compared using the Chi-square test. Results: There were significant differences in the frequency of the PTPN22 1858T polymorphism in the URPL individuals vs. the healthy controls, i.e. 32.0% and 21.5%, respectively (p = 0.01). Conclusion: Our findings suggest that the PTPN22 1858T polymorphism could play a role in recurrent pregnancy loss. Therefore, genotyping of the mentioned polymorphism can help clinicians to predict the probable risk of URPL. Key words: Recurrent pregnancy loss, PTPN22 protein, Single nucleotide polymorphism.

Association of PTPN22 single nucleotide polymorphisms with chronic spontaneous urticaria

Introduction and objectives: Chronic spontaneous urticaria (CSU) is thought to be an auto-immune disease in a subpopulation of patients. Protein tyrosine phosphatase-22 (PTPN22) polymorphisms are considered to be one of the strongest contributing factors to autoimmune diseases. In this study, we aimed to investigate the potential association of several PTPN22 single nucleotide polymorphisms (SNPs) with CSU in an Iranian population.Material and methods: A total of 93 CSU patients and 100 healthy individuals were included in this study. Five SNPs within the PTPN22 gene were analyzed using TaqMan genotyping assays. The frequency of alleles, genotypes, and haplotypes of PTPN22 SNPs (rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649) was investigated.Results: A significantly higher prevalence of the rs1310182 T allele was observed among patients compared with controls [OR = 1.75 (95% CI: 1.17–2.63); P = 0.007]. In addition, the rs1310182 CC genotype and TT genotype were 0.47 and 2.06 times more common in patients, respectively (P = 0.03). Moreover, haplotype analysis demonstrated that CGCGC, CGTGC, and TGCGC (P < 0.001) were significantly associated with CSU. No significant differences were observed between the patients and controls in the other analyzed PTPN22 SNPs.Conclusions: Polymorphisms of the PTPN22 gene are associated with an increased susceptibility to CSU in the studied Iranian population.