Association of the gene encoding the δ-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis

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 d-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 ¼ 0.0154). This allele was also over-represented in a group of 350 unrelated nonthymoma MG patients (OR ¼ 1.78, P ¼ 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 ¼ 2.07, P ¼ 0.017). In contrast, there was no distortion in the transmission of a single-nucleotide substitution polymorphisms (SNPs) in the 3 0 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.

Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis

“…8,12 Although still little is known about genetic factors associated in nonthymoma patients with anti-titin antibodies and in thymoma patients, the group of nonthymoma patients with an early onset of disease and lacking anti-titin antibodies demonstrates a remarkable association with HLA genes, 8,12,13,15 and also with loci encoding the AChR. 17,18 Such an association with a particular genetic makeup supports the concept that this group of patients corresponds to an etiologically distinct disease entity. In this context, the fact that the R620W polymorphism is functional provides an invaluable lead in the search for and the identification of other molecular variants that contribute to individual disease susceptibility in this characteristic form of MG. OR ϭ odds ratio; CI ϭ confidence interval.…”

Thermo‐hygro‐mechanical behavior of spider dragline silk: Glassy and rubbery states

“…Our data document a genetic heterogeneity of MG that closely parallels the well‐established clinical and biological heterogeneity of the disease 8, 12. Although still little is known about genetic factors associated in nonthymoma patients with anti‐titin antibodies and in thymoma patients, the group of nonthymoma patients with an early onset of disease and lacking anti‐titin antibodies demonstrates a remarkable association with HLA genes,8, 12, 13, 15 and also with loci encoding the AChR 17, 18. Such an association with a particular genetic makeup supports the concept that this group of patients corresponds to an etiologically distinct disease entity.…”

Identifying the culprits in neurological autoimmune diseases

“…Polymorphisms in this gene (i.e. rs1004432, rs1550093, and rs2767) disrupt a transcription binding motif [ 46 ]. The frequency of the variant FcγRIIa-R/R131 is higher in MG patients, and it modifies B-cell activation and clears ineffectively small AChR IgG complexes [ 47 ].…”