Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population

Objectives The purpose of this case-control study was to investigate whether polymorphisms and gene-gene interactions of the two type I interferon (IFN) genes (IRF5 and TYK2) are the susceptible factors of systemic Lupus erythematosus (SLE) in the Han Chinese population. Methods The four variants [rs2004640, rs2070197, rs10954213 and exon6 insertion/deletion (in/de)] of IRF5 gene and five single-nucleotide polymorphisms (SNPs) (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 gene were examined in a cohort of 642 SLE patients and 642 healthy controls. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing in 10 % sample randomly. Results Rs2070197 was not polymorphic in this study, and was excluded in further analysis. Significant association was found for loci on IRF5 (rs2004640: p = 0.0003, p (corr) = 0.0012) and TYK2 (rs280500: p = 8.83 x 10(-6), p (corr) = 4.41 x 10(-5); rs2304256: p = 3.71 x 10(-6), p (corr) = 1.85 x 10(-5); rs8108236: p = 0.0004, p (corr) = 0.002), but not for other SNPs. Significant association was also observed for genotypes of IRF5 (rs2004640, p = 0.0009, p (corr) = 0.0036) and TYK2 SNPs (rs280500: p = 5.21 x 10(-5), p (corr) = 2.61 x 10(-4); rs2304256: p = 7.72 x 10(-6), p (corr) = 3.86 x 10(-5); rs8108236: p = 0.002, p (corr) = 0.01). Nevertheless, two haplotypes based on the 3 variants [exon6(in/de), rs10954213, rs2004640] of IRF5 (DAG and IAT) could define protective or susceptibility haplotype in SLE. Similarly, three haplotypes containing 5 SNPs (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 (GATAT, AGGAT and GAGGT) may also be associated with SLE in Han Chinese. Additionally, the gene-gene interaction analysis was conducted on the IRF5 and TYK2 SNPs. And a three-way interaction between TYK2 rs280500, rs2304256 and IRF5 rs10954213 and SLE was found (p < 0.0001). Conclusions Genetic associations and gene-gene interactions of IRF5 and TYK2 were significantly detected in Han Chinese with SLE. Our results had important implications for future research on the role of type I IFN function in SLE susceptibility.