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

Abstract

Interleukin 1 (IL-1) β Taq I 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-1 β Taq I 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-1 β Taq I 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-1 β Taq I 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-1 β and a possible intrinsic dyregulation of IL-1 in MG.