title: 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.
authors.affiliation: School of Nutrition and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Mahmoudi
authors.forename: F
authors.initials: F
authors.lastname: Tahghighi
authors.forename: V
authors.initials: V
authors.lastname: Ziaee
authors.forename: S
authors.initials: S
authors.lastname: Harsini
authors.forename: A
authors.initials: A
authors.lastname: Rezaei
authors.forename: S
authors.initials: S
authors.lastname: Soltani
authors.forename: M
authors.initials: M
authors.lastname: Sadr
authors.forename: M H
authors.initials: MH
authors.lastname: Moradinejad
authors.forename: Y
authors.initials: Y
authors.lastname: Aghighi
authors.forename: N
authors.initials: N
authors.lastname: Rezaei
mesh_terms: D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics
chemical_list: C508598:IL4 protein, human; D019948:Receptors, Interleukin-4; D015847:Interleukin-4