Polymorphisms in IL-1β and IL-1 receptor antagonist genes are associated with myasthenia gravis

Interleukin 1 (IL-1)beta, TaqI restriction fragment length polymorphism (RFLP) in exon 5 and IL-1 receptor antagonist (IL-1Ra) polymorphism, variable numbers of an 86-bp tandem repeat (VNTR), were analysed in 107 patients with myasthenia gravis (MG) and 82 ethnically matched healthy control (HC) individuals. Positive association was found with IL-1beta TaqI RFLP allele 2 carriage in MG (OR = 2.007), while allele 1 was negatively associated with MG (OR = 0.498). When homozygous individuals for allele 2 were considered, the association was stronger (OR = 4.630), indicating a dose effect of allele 2. Analysis of IL-1beta TaqI RFLP in relation to HLA-B8 demonstrated that the allelic association was more pronounced in patients without HLA-B8 (OR = 2.813). There was no difference in IL-1Ra VNTR allelic distribution in MG patients compared with HC. However, MG patients who were noncarriers of IL-Ra allele 2 had a significantly higher percentage of IL-1beta TaqI RFLP allele 2 carriage (OR = 3.085), while there was no such difference in IL-1Ra allele 2 carriers. Our results demonstrate a new genetic marker in MG, which exerts its maximum effect in patients with the lowest MHC-associated susceptibility. We propose a possible pathogenetic role of IL-1beta and a possible intrinsic dyregulation of IL-1 in MG.