Abstract
The muscle acetylcholine receptor (AChR) is the main target self-antigen in acquired autoimmune myasthenia gravis (MG). Here, we investigated an association of MG with the CHRND gene encoding the δ-subunit of the AChR. Using a microsatellite repeat located in the second intron of the gene, we observed a preferential transmission of the allele 268 in 114 one-generation families with one myasthenic child (Pc=0.0154). This allele was also over-represented in a group of 350 unrelated nonthymoma MG patients (OR=1.78, P=0.038), but not in 84 thymoma patients, compared to 168 healthy controls. Moreover, among nonthymoma patients, those lacking serum anti-titin antibodies appeared to be best associated (OR=2.07, P=0.017). In contrast, there was no distortion in the transmission of a single-nucleotide substitution polymorphisms (SNPs) in the 3′ untranslated region of CHRND nor in that of two SNPs located in the closely linked CHRNG gene, 4.5 kb telomeric to CHRND. The data warrant a detailed investigation of CHRND polymorphism in MG patients.
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Acknowledgements
This study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and by the Association Française contre les Myopathies. MG is a fellow of the Ministère de la Recherche. We are most grateful to Ms Claudia de Toma (Fondation Jean Dausset – Centre d’Etude du Polymorphisme Humain, Paris) for her generous gift of control DNA samples. We thank Guy Fluteau for his technical help.
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Giraud, M., Eymard, B., Tranchant, C. et al. Association of the gene encoding the δ-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis. Genes Immun 5, 80–83 (2004). https://doi.org/10.1038/sj.gene.6364041
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DOI: https://doi.org/10.1038/sj.gene.6364041