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

Inflammation research : official journal of the European Histamine Research Society ... [et al.]

PubMedID: 26294277

Tang L, Wan P, Wang Y, Pan J, Wang Y, Chen B. Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population. Inflamm Res. 2015;.
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 × 10(-6), p corr  = 4.41 × 10(-5); rs2304256: p = 3.71 × 10(-6), p corr  = 1.85 × 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 × 10(-5), p corr  = 2.61 × 10(-4); rs2304256: p = 7.72 × 10(-6), p corr  = 3.86 × 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.