Interleukin‐4 single nucleotide polymorphisms in juvenile systemic lupus erythematosus

Abstract

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.

Cytokines in systemic lupus erythematosus: their role in pathogenesis of disease and possible therapeutic opportunities

“…It seems the role of IL4 in SLE is dependent on genetic background. Some studies showed that IL4 gene polymorphisms might be involved in the etiology and susceptibility of SLE (50,51). We showed in our recent study on JSLE patients that IL-4 gene variants are associated with JSLE and might have a role in the pathophysiology of disease (50).…”

“…Some studies showed that IL4 gene polymorphisms might be involved in the etiology and susceptibility of SLE (50,51). We showed in our recent study on JSLE patients that IL-4 gene variants are associated with JSLE and might have a role in the pathophysiology of disease (50). An association between polymorphisms of interleukin-4 gene and discoid rash was reported in Chinese patients with SLE (52).…”

The Role of the Transcription Factor Ets1 in Lupus and Other Autoimmune Diseases

“…146 IL-4 is elevated in some human SLE patients 147,148 and SNPs in the IL-4 locus are associated with increased susceptibility to lupus. 149,150 In keeping with increased levels of Th2 cytokines in vivo in Ets1 −/− mice, B cells from these animals show increased isotype-switching to IgG1 and IgE and increased numbers of plasma cells ( 18,77 and unpublished data). Although it is not yet clear whether the IgG1 or IgE produced by Ets1 −/− mice is pathogenic, it is interesting to note that pathogenic IgE autoantibodies have recently been described in Lyn knockout mice that share many similar phenotypic features with Ets1 knockout mice (see above).…”

PDCD1single nucleotide genes polymorphisms confer susceptibility to juvenile-onset systemic lupus erythematosus

“…Nevertheless, most of the association studies have focused mainly on patients with adult-onset SLE. To the best of our knowledge, there are only a few number of genetic studies on juvenile-onset SLE [2,3,[20][21][22][23]. In this study, we have evaluated a group of Iranian patients with JSLE for the PD1.1, PD1.3 and PD1.9 SNPs.…”