The 1858T PTPN22 Gene Variant Confers Sex-Biased Susceptibility to Type 1 Diabetes; an Evaluation in Children and Adolescents of Egyptian origin

BACKGROUND AND OBJECTIVES: Type 1 diabetes "T1D" is a multigenic autoimmune disease with over 60 susceptibility loci identified. A PTPN22 C1858T single nucleotide polymorphism "SNP" has been implicated as a major contributor in the predisposition of T1D in different populations. Our aim was to evaluate the impact of such genetic variability in the pathogenesis of T1D in Egyptian patients. RESEARCH DESIGN: In a retrospective study design and after full clinical and laboratory investigations for our subjects, DNA was extracted and genotyped for PTPN22 +1858 C>T (rs2476601) SNP analysis in 85-clinically diagnosed unrelated patients with T1D and 65- age, sex and BMI matched healthy controls using a real-time PCR TaqMan® sequence-specific probe-based 5?allelic discrimination assay. RESULTS: Logistic regression analysis confirms the association of the PTPN22 C1858T polymorphic site with T1D [P-value = 0.0012; OR = 4.58 at 95% CI = 1.76 – 11.91]. Additionally, the minor 1858T allele is related to the disease in a female sex-specific manner (P-value = 0.001) with an increase in the OR = 8.12 at 95%CI = 2.14 - 30.78. CONCLUSION: The PTPN22 1858T variant might play a pivotal role in the pathogenesis of T1D in Egyptian population by a gender-dependent mechanism that contributes to unique predisposition in females. Furthermore, neither age at disease onset nor susceptibility to diabetic nephropathy "DN" is conferred by the high-risk mutant allele.