Interleukin-4 single nucleotide polymorphisms in juvenile systemic lupus erythematosus

• Published in: International journal of immunogenetics Vol. 41; no. 6; pp. 512 - 517
• Main Authors: Mahmoudi, M., Tahghighi, F., Ziaee, V., Harsini, S., Rezaei, A., Soltani, S., Sadr, M., Moradinejad, M. H., Aghighi, Y., Rezaei, N.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-12-2014
• Subjects: Case-Control Studies; Child; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Interleukin-4 - genetics; Lupus Erythematosus, Systemic - genetics; Male; Polymorphism, Single Nucleotide - genetics; Receptors, Interleukin-4 - genetics
• ISSN: 1744-3121; 1744-313X
• DOI: 10.1111/iji.12152

Summary
Juvenile systemic lupus erythematosus (JSLE) is a chronic, recurrent multisystem inflammatory disease, caused by a combination of environmental events and genetic risk factors. As cytokines, including interleukin‐4 (IL‐4), seem to have a role in the pathogenesis of JSLE, the investigation was performed to evaluate the associations of specific single nucleotide polymorphisms (SNPs) of IL‐4 and IL‐4RA genes in a case–control study. Fifty‐nine patients with JSLE were recruited in this study as patients' group and compared with 140 healthy volunteers. Genotyping was performed for IL‐4 gene at positions −1098, −590 and −33, as well as IL‐4 receptor α (IL‐4RA) gene at position +1902, using polymerase chain reaction with sequence‐specific primers method. Following alleles were found to be more common among patients with JSLE: C at −590 and −33 and T at −1098 of IL‐4 gene (P value < 0.001; OR = 4.6, P value < 0.001; OR = 2.7 and P value < 0.001; OR = 2.1, respectively). Additionally, significant positive associations for the following genotypes were recognized in JSLE cases, compared with controls: C/C at −33, C/C at −590 and T/T at −1098 of IL‐4 gene (P value < 0.001; OR = 5.3, P value < 0.001; OR = 29.5 and P value < 0.001; OR = 3.3, respectively), while following genotypes were less frequent among patients with JSLE: T/C at −33 and −590 and T/G at −1098 of IL‐4 gene (P value < 0.001; OR = 0.1, P value < 0.001; OR = 0.03 and P value < 0.001; OR = 0.3, respectively). Furthermore, we noticed an astonishing negative haplotypic association for JSLE for IL‐4 (positions −1098, −509 and −33) TTC, GCC and TTT haplotypes (P value < 0.001). There was also a significant relationship between TCC haplotype (IL‐4 gene at positions −1098, −590 and −33) and having JSLE (P value < 0.001). On the other hand, we found no significant associations between IL‐4R polymorphisms and the susceptibility to JSLE. Cytokine gene polymorphisms may influence susceptibility to JSLE. Particular IL‐4 gene variants are associated with JSLE and might have a role in the pathophysiology of disease.