Giraud M, Eymard B, Tranchant C, Gajdos P, Garchon H-J
INSERM U580, Hôpital Necker, Paris, France.
Genes Immun. 2004 Jan;5(1):80-3. doi: 10.1038/sj.gene.6364041.
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 delta-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.
肌肉乙酰胆碱受体（AChR）是获得性自身免疫性重症肌无力（MG）的主要靶自身抗原。在此，我们研究了MG与编码AChRδ亚基的CHRND基因之间的关联。利用位于该基因第二内含子中的微卫星重复序列，我们在114个有一个患重症肌无力子女的一代家庭中观察到等位基因268的优先传递（Pc = 0.0154）。与168名健康对照相比，该等位基因在350名无关的非胸腺瘤MG患者组中也过度表达（OR = 1.78，P = 0.038），但在84名胸腺瘤患者中未出现这种情况。此外，在非胸腺瘤患者中，那些缺乏血清抗肌动蛋白抗体的患者似乎关联最为密切（OR = 2.07，P = 0.017）。相比之下，CHRND基因3'非翻译区的单核苷酸替代多态性（SNP）以及位于与CHRND基因紧密连锁的CHRNG基因（位于CHRND基因端粒方向4.5 kb处）中的两个SNP在传递过程中均未出现偏差。这些数据表明有必要对MG患者的CHRND多态性进行详细研究。
