Genetic Association of Interkeukin-21 and Interleukin-23 Receptor Polymorphisms With Systemic Lupus Erythematosus in Iranian Population

Objective: T helper 17 (Th17) is believed to play a crucial role in pathophysiology of systemic lupus erythematosus (SLE). Our study aimed to detect the potential association of IL-21 and IL-23R polymorphisms with susceptibility to SLE. Method: Two hundreds and ten patients with SLE and the same number of matched controls were genotyped by polymerase chain reaction to detect two polymorphisms of IL-21 and one polymorphism of IL-23 receptor (IL-23R). Clinical data was collected from patients’ archives. Results: IL-21 polymorphisms (rs4833837 C/T and rs2055979 G/T) did not show any association with the disease susceptibility (p= 0.54 and p= 0.49, respectively). Comparison of patients with rs2055979GG and T allele carriers showed higher frequency of rs2055979GG genotype in patients with pleurisy compared to the ones without pleurisy (p=0.004). In addition, categorization of IL-23R rs10889677 to GG and T allele carriers (TT+TG) showed an association between TT+TG genotypes and susceptibility to SLE (p=0.0002). Moreover, a significant association was found between the inheritance of rs10889677GG+TG genotypes and presence of mucosal ulcers in SLE patients (p=0.01). Discussion: The results showed that the lower IL-21 producer rs2055979GG genotype was associated to pleurisy. Lower IL-21 serum levels in patients with rs2055979GG genotype may lead to more frequent pulmonary infections and an increased risk of pleurisy. Association of high+ intermediate IL-23R producer genotypes (rs10889677TT+TG) with SLE may be explained by possible overactivation of Th17 cells. Higher activity of Th17 cells may also explain the over representation of mucosal ulcer in patients with high producer genotype of IL-23R.