Journal of Inflammation Research (Jul 2021)
Genetic Polymorphisms in Genes Involved in the Type I Interferon System (IFIH1/MDA-5, TNFAIP3/A20, and STAT4): Association with SLE Risk in Egyptian Children and Adolescents
Abstract
Mohamed M Zedan,1 Zeinab Rizk Attia,2 Rania A Abd El Azeem,2,3 Thuraya M Mutawi,2 Amora S El Shehawy,1 Ashraf Bakr1 1Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 2Department of Laboratories, Immunology Lab, Mansoura University Children’s Hospital, Mansoura University, Mansoura, Egypt; 3Department of Clinical Laboratory Sciences, College of Medical Applied Sciences, University of Hafr Al Batin, Hafr Al Batin, Saudi ArabiaCorrespondence: Zeinab Rizk AttiaDepartment of Laboratories, Immunology Lab, Mansoura University Children’s Hospital, Mansoura University, 60 Elgomhoria Street, Mansoura, 35516, EgyptTel +201098830190Email [email protected]: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune inflammatory disease that is influenced by both genetic and environmental factors and associated with dysregulation of type I interferon (INF) response. This study aimed to investigate the effects of single nucleotide polymorphisms (SNPs) of the IFIH1, TNFAIP3, and STAT4 genes in the type I INF system on SLE risk in Egyptian children and adolescents.Patients and Methods: We recruited 94 SLE individuals and 94 healthy subjects. SNPs of IFIH1 rs3747517 C/T, TNFAIP3 rs610604 G/T, and STAT4 rs7574865 G/T were evaluated using TaqMan™ SNP genotyping assay.Results: Individuals with the TT, CT+TT genotypes, and T allele of rs3747517 in the IFIH1 gene were protective for SLE patients (OR = 0.429, 95% CI = 0.191– 0.962, P = 0.040), (OR = 0.685, 95% CI = 0.477– 0.984, P = 0.041), and (OR = 0.705, 95% CI = 0.527– 0.944, P = 0.019), respectively. Also, individuals with the TT, GT+TT genotypes, and T allele of rs7574865 in the STAT4 gene were associated with SLE risk (OR = 3.945, 95% CI = 1.303– 11.947, P = 0.015), (OR = 1.536, 95% CI = 1.058– 2.231, P = 0.024), and (OR = 1.522, 95% CI = 1.113– 2.082, P = 0.009), respectively. In the case of TNFAIP3 rs610604, no significant association of genotypes or alleles with SLE were detected, while the three SNPs did not show any significant association with the SLE clinical or laboratory features.Conclusion: Our findings indicated that rs3747517 in IFIH1 was protective for SLE in Egyptian children and adolescents. Moreover, rs7574865 in STAT4 not rs610604 in TNFAIP3 was associated with SLE risk.Keywords: systemic lupus erythematosus, type I interferon system, autoimmune disease, genetic polymorphism
