POLYMORPHISMS IN IL-1-BETA AND IL-1 RECEPTOR ANTAGONIST 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 10 7 patients with myasthenia gravis (MG) and 82 ethnically matched healt hy control (HC) individuals. Positive association was found with IL-1 beta TagI RFLP allele 2 carriage in MG (OR = 2.007), while allele 1 wa s negatively associated with MG (OR = 0.498). When homozygous individu als for allele 2 were considered, the association was stronger (OR = 4 .630). indicating a dose effect of allele 2. Analysis of IL-1 beta 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 wa s no difference in IL-1Ra VNTR allelic distribution in MG patients com pared with HC. However. MG patients who were noncarriers of IL-Ra alle le 2 had a significantly higher percentage of IL-1 beta TagI RFLP alle le 2 carriage (OR = 3.085), while there was no such difference in IL-1 Ra allele 2 carriers. Our results demonstrate a new genetic marker in MG, which exerts its maximum effect in patients with the lowest MHC-as sociated susceptibility. We propose a possible pathogenetic role of IL -1 beta and a possible intrinsic dyregulation of IL-1 in MG. (C) 1998 Elsevier Science B.V.