Interleukin 1 receptor type 1 gene variants associate with disease susceptibility to IgG4-related periaortitis/periarteritis in IgG4-related disease

Abstract Background IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system. Since the genetic factors related to disease onset are unclear, we examined the genetic associations with IgG4-related periaortitis/periarteritis susceptibility. Methods A recent genome-wide association study identified interleukin 1 receptor type 1 (IL1R1) gene variants in 75 patients with IgG4-RD. Accordingly, 8 single nucleotide polymorphisms (SNPs) in the IL1R1 gene were selected and genotyped in 124 patients with IgG4-RD (43 with IgG4-related periaortitis/periarteritis) and 344 healthy subjects. Serum IL-1β levels were also determined in 102 IgG4-RD patients. Results No remarkable SNP associations were detected between IgG4-RD patients and controls. However, the minor allele frequencies of 6 SNPs (rs2287049, rs3917273, rs2160227, rs951192, rs3917318, and rs7582198) were significantly increased in IgG4-related periaortitis/periarteritis patients (corrected P < 0.05). Serum IL-1β levels were significantly lower in patients with IgG4-related periaortitis/periarteritis (P = 0.011) but were not associated with any SNP. Conclusions This study indicated that IL1R1 SNPs contributed to IgG4-related periaortitis/periarteritis, but not IgG4-RD, onset. Our findings raise the possibility of certain genetic factors influencing the risk of specific IgG4-RD manifestations.