Impact of the IL-17F, IL-23 and IL-23R on susceptibility and phenotype of systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a disease characterized by excessive proinflammatory cytokine production and damage to multiple organ systems. To investigate the potential association between cytokine gene polymorphisms and SLE, we performed a case-control study based on Polish population. SLE patients and controls, were examined for IL-23A rs11171806 G/A and IL-23R (rs1884444 G/T, rs10489629 G/A) by TaqMan SNP genotyping assay, for IL-17F rs763780 A/G and rs2397084A/G using the PCR– RFLP method. An increased frequency of AG genotype as well as G allele of the IL-17F rs763780 was found in patients with SLE, as compared with healthy subjects (OR = 3.947; p = 0.001 and OR = 3.538; p = 0.002, respectively). Frequencies of the rs1884444 TT genotype (OR = 138.1) and the rs1884444 T allele (OR = 2.176) were also higher in SLE patients (both p < 0.0001). Overall, weak LD was observed between the IL-17F rs763780 A/G and rs2397084 A/G polymorphisms (D'-0.003, r² – 0.000). From four possible haplotypes, frequencies of AG showed differences between both examined groups (p < 0.0001). We also observed a weak LD between the IL-23R rs10489629G/A and rs1884444 G/T (D'-0.199, r² –0.026). The genotype–phenotype analysis showed significant association between the IL-17F rs2397084 and mean value of the hemoglobin (p = 0.01), the IL-17F rs763780 and age (p = 0.008) and lupus anticoagulant (p = 0.09), the IL-23 rs11171806 and urea (p = 0.08) and C3 complement (p = 0.03), and the IL-23R rs1884444 G/T and activated partial thromboplastin time (p = 0.06). Present findings indicated that IL-17F rs763780 A/G and IL-23R rs1884444 G/T polymorphisms may be involved in susceptibility to SLE in the Polish population.

• Association study
• cytokine
• pathogenesis
• polymorphisms
• SLE

Acknowledgements

The technical assistance of Mr. Agnieszka Hertel, Wieslawa Frankowska and Teresa Golaszewska is gratefully acknowledged. The authors are also grateful to all of the SLE patients whose cooperation made this study possible.

Declaration of interest

The authors declare no conflict of interest. This study was supported by grant No 502-01-01124182-07474, Poznań University of Medical Sciences.