TNFA and TNFB polymorphisms in myasthenia gravis.
BACKGROUND
Tumor necrosis factor (TNF) alpha and TNF-beta are proinflammatory cytokines thought to be involved in the pathogenesis of myasthenia gravis (MG).


OBJECTIVE
To examine whether TNF polymorphisms are associated with MG, MG subgroups, and the presence of titin and ryanodine-receptor antibodies.


METHODS
We did genotyping on 30 patients with MG and 92 healthy blood donors for 2 biallelic TNFA polymorphisms (G to A at positions -238 and -308) and 1 TNFB polymorphism (NcoI digestive site) using methods based on the polymerase chain reaction.


RESULTS
Patients with thymoma were typically homozygous for both the TNFA*T1 and the TNFB*2 alleles, but patients having an early onset of MG without thymoma were carriers of the TNFA*T2 and TNFB*1 alleles. Patients without thymoma who had the titin antibody had the same high frequency of TNFA*T1 and TNFB*2 as patients with thymoma, whereas patients without the titin antibody carried the same allele, TNFA*T2 and TNFB*1, regardless of age and thymic disease. No association was found with acetylcholine-receptor levels or disease severity for any of the TNFA or TNFB polymorphisms.


CONCLUSIONS
Patients having MG, including those with thymoma, who have the titin antibody are most often homozygous for the TNFA*T1 and TNFB*2 alleles, whereas the presence of the TNFA*T2 and TNFB*1 alleles correlates with early-onset MG and the absence of titin antibodies.
Skeie
G O
GO
Department of Neurology, Haukeland Hospital, University of Bergen, Norway.
Pandey
J P
JP
Aarli
J A
JA
Gilhus
N E
NE
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000595:Amino Acid Sequence; D064211:Connectin; D005260:Female; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000276:immunology; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000276:immunology; D013945:Thymoma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D064211:Connectin; D008233:Lymphotoxin-alpha; D009124:Muscle Proteins; C577285:TTN protein, human; D014409:Tumor Necrosis Factor-alpha; D011494:Protein Kinases