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.

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 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.

CONCLUSION

Specific combinations of allelic variants individually associated with MG synergize in predisposing to thymomatous MG and MG with titin antibodies.