The genetic influence of PD-1/PD-L1 axis single nucleotide polymorphisms on the incidence of type 1 diabetes mellitus in pediatric Egyptian patients

Abstract

Background The increasing prevalence of diabetes mellitus (DM) is one of the most challenging public health issues. The destruction of insulin-producing cells in the islets of Langerhans is the hallmark of type 1 diabetes mellitus (T1DM) as an autoimmune disease. In the current case–control study, the role of single nucleotide polymorphisms (SNPs) was investigated within the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitory axis and their association with T1DM susceptibility in a sample of Egyptian pediatric patients. The study included 80 T1DM pediatric patients and 76 healthy control subjects. The patients were recruited from Beni-Suef University Hospital’s Pediatric Endocrinology Outpatient Clinic. Genotyping of PD-1 SNP (rs 34819629) and PD-L1 SNPs (rs 2297137 and rs 4143815) was performed by TaqMan allelic discrimination technique via real-time polymerase chain reaction (RT-PCR). The patients were subjected to a thorough clinical examination and history taking. Result Genotyping of PD-1 (rs 34819629) revealed that all of the enrolled patients and the control group inherited the same genotype (GG genotype). With regard to PDL-1 rs4143815 SNP and the risk of T1DM occurrence, our comparison did not reveal the presence of an association between the different genetic models (general, dominant, and recessive) of the SNP and the risk of T1DM (p = 0.078 and p = 0.055; for the general genetic model, p = 0.061 and p = 0.169 for the dominant and the recessive types, respectively). Regarding PDL-1 rs2297137 SNP, the results of this study demonstrated that the risk of T1DM was significantly associated with the recessive genetic model (p = 0.007) as the diabetic group’s predominant G allele was higher compared to the control group. Conclusion The findings obtained supported the hypothesis that the predominant G allele of PD-L1 rs2297137 is associated with the development of T1DM. Chronic hyperglycemia and long-standing diabetes problems are linked to both PD-L1 SNPs (rs4143815 and rs2297137). Future studies with a more significant number of patients are required to support our results.