Polygenic disease associations in thymomatous myasthenia gravis.
BACKGROUND
Relevant genetic markers for myasthenia gravis (MG) include tumor necrosis factors alpha and beta, Fcgamma receptor IIa, and interleukin 10. The corresponding gene products are thought to be involved in MG pathogenesis.


OBJECTIVE
To investigate whether MG susceptibility correlates with specific combinations of genetic markers and to compare the contribution of each marker.


METHODS
Forty-seven patients with MG and 92 healthy blood donors.


METHODS
Presence of tumor necrosis factors alpha and beta, Fcgamma receptor IIa, and interleukin 10 genotypes and autoantibodies against nicotinic acetylcholine receptor, titin, and ryanodine receptor.


RESULTS
Susceptibility to MG increases with an increasing number of genetic markers in both thymomatous MG and MG with titin antibodies but not in early-onset MG. In thymomatous MG, Fcgamma receptor IIa allelic variants seem to be the most important determinant of disease.


CONCLUSIONS
Specific combinations of allelic variants individually associated with MG synergize in predisposing to thymomatous MG and MG with titin antibodies.
Amdahl
Christian
C
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Alseth
Espen H
EH
Gilhus
Nils E
NE
Nakkestad
Hanne L
HL
Skeie
Geir O
GO
D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D001323:Autoantibodies / Q000032:analysis; D064211:Connectin; D004247:DNA / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D009124:Muscle Proteins / Q000276:immunology; D009157:Myasthenia Gravis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011494:Protein Kinases / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics; D011978:Receptors, Nicotinic / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000276:immunology; D013945:Thymoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013953:Thymus Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D001323:Autoantibodies; D064211:Connectin; C080568:Fc gamma receptor IIA; D005819:Genetic Markers; D008233:Lymphotoxin-alpha; D009124:Muscle Proteins; D017452:Receptors, IgG; D011978:Receptors, Nicotinic; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004247:DNA; D011494:Protein Kinases