Polymorphisms in IL-1beta 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.
Huang
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Immunological Research Unit, Center of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Pirskanen
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R
Hjelmström
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Lefvert
A K
AK
D000328:Adult; D000483:Alleles; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific; D004198:Disease Susceptibility; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D015795:HLA-B8 Antigen / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009157:Myasthenia Gravis / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012795:Sialoglycoproteins / Q000235:genetics*
D005819:Genetic Markers; D015795:HLA-B8 Antigen; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases