IRAK2 is associated with systemic lupus erythematosus risk

Introduction: Interleukin-1 receptor-associated kinases (IRAKs) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways. They play a key role in inflammation and innate immunity. IRAKs have been previously incriminated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis and inhibition of IRAKs has been recently regarded as a potential therapeutic strategy for SLE.

Objectives: The aim of the present study was to test the association between IRAK2 rs708035 and rs3844283 with SLE.

Material and methods: IRAK2 rs708035 and rs3844283 were genotyped by mutagenically separated polymerase chain reaction (MS-PCR) in 142 SLE patients and 149 age- and gender-matched controls.

Results: The hyperfunctional IRAK2 rs708035 A allele was more frequent among SLE patients than controls (62.9% versus 54.7%, p = 0.046). IRAK2 rs3844283 C allele was present in 66.5% of patients and 75.5% of controls. The CC genotype was the most frequently exhibited genotype. It was carried by 45.1% of patients with SLE and 57.7% of controls. The G allele was associated with an increased risk of SLE (OR = 1.54, 95%, CI = 1.07-2.22, p = 0.017). IRAK2 rs708035 and IRAK2 rs3844283 were in linkage disequilibrium (D' = 0.64). The AG haplotype was more frequently observed in SLE patients than in controls (0.292 versus 0.194, p = 0.008).

Conclusion: This study for the first time ever reveals the association of IRAK2 rs708035 and IRAK2 rs3844283 and the corresponding haplotypes with SLE. Our findings give additional rationale to target IRAKs in the treatment of SLE.Key Points• IRAK2 rs708035 A allele is more frequent in SLE patients than in controls and IRAK2 rs3844283 G allele is associated with SLE susceptibility.• These two alleles are in linkage disequilibrium.• The AG haplotype is associated with SLE.