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Polygenic Disease Associations in Thymomatous Myasthenia Gravis
Christian Amdahl;
Espen H. Alseth;
Nils E. Gilhus, MD, PhD;
Hanne L. Nakkestad;
Geir O. Skeie, MD, PhD
Arch Neurol. 2007;64(12):1729-1733.
Background Relevant genetic markers for myasthenia gravis (MG) include tumor necrosis factors  and β, Fc receptor IIa, and interleukin 10. The corresponding gene products are thought to be involved in MG pathogenesis.
Objectives To investigate whether MG susceptibility correlates with specific combinations of genetic markers and to compare the contribution of each marker.
Participants Forty-seven patients with MG and 92 healthy blood donors.
Main Outcome Measures Presence of tumor necrosis factors and β, Fc 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, Fc receptor IIa allelic variants seem to be the most important determinant of disease.
Conclusion Specific combinations of allelic variants individually associated with MG synergize in predisposing to thymomatous MG and MG with titin antibodies.
Author Affiliations: Department of Clinical Medicine, University of Bergen (Messrs Amdahl and Alseth, Drs Gilhus and Skeie, and Ms Nakkestad), and Department of Neurology, Haukeland University Hospital (Drs Gilhus and Skeie), Bergen, Norway.
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