Novel polymorphism of IFI44L associated with the susceptibility and clinical characteristics of systemic lupus erythematosus in a Chinese population

Background: Interferon-inducible 44 like (IFI44L) is a newly discovered gene which has been reported to associate with the susceptibility of some infectious diseases, but there is no data on IFI44L SNP polymorphism associated with Systemic lupus erythematosus (SLE). In this study, we aimed to evaluate the association of IFI44L rs273259 polymorphism with the susceptibility and clinical characteristics of SLE in a Chinese population.

Methods: 576 SLE patients and 600 controls were recruited in this case-control study. Blood DNA was extracted and IFI44L rs273259 polymorphism was detected by TaqMan SNP Genotyping Assay Kit. The expression levels of IFI44L in Peripheral blood mononuclear cells were detected by RT-qPCR. The DNA methylation levels of IFI44L promoter were detected by bisulfite pyrosequencing.

Results: The genotype and allele frequencies of IFI44L rs273259 in SLE patients have a significantly difference compared to healthy controls (P < 0.001). The genotype AG (vs. AA: OR = 2.849; P < 0.001) and the allele G (vs. A: OR = 1.454; P < 0.001) were associated with increased susceptibility of SLE. IFI44L rs273259 polymorphism was associated with clinical characteristics of SLE including malar rash (P < 0.001), discoid rash (P < 0.001), lupus nephritis (P < 0.001) and anti-Smith antibodies (P < 0.001). The expression levels of IFI44L were most significantly increased in genotype AG than genotype AA and GG (P < 0.01). The DNA methylation levels of IFI44L promoter were most significantly decreased in genotype AG than genotype AA and GG (P < 0.01).

Conclusions: Our results indicate novel polymorphism of IFI44L rs273259 was associated with the susceptibility and clinical characteristics of SLE in the Chinese population.