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Abnormal CTLA-4 expression is involved in the development of myasthenia gravis (MG), and serum CTLA-4 levels are positively correlated with serum anti-AChR antibody concentration, which might be related with the severity of MG. Polymorphism in CTLA-4 gene is associated with various autoimmune disorders. We investigated the association of polymorphism in CTLA-4 gene with the clinical variables and severity of MG. The frequencies of alleles and genotypes were compared between 480 MG patients and 487 healthy controls, as well as among subgroups of MG patients. The frequency of rs733618*C allele is significantly higher in MG group and several subgroups than in control group. Genotype is not found as independent factor for essential clinical variables of MG. The frequency of rs231775*A allele is significantly lower in ocular onset subgroup than in control group, and the frequencies of rs231775*A allele and rs3087243*A allele are significantly lower in ocular onset subgroup than in generalized onset subgroup. Genotypes of the two SNPs are found as independent factors for ocular onset. The frequency of rs231775*A allele is significantly lower in mild subgroup than that in control group. Genotype is not found as independent factor for mild severity. A haplotype containing rs733618*C, rs231775*G and rs3087243*G is identified to increase the general risk of MG by 1.278-fold and ocular onset MG subgroup by 1.362-fold. There is association of rs733618 with the general susceptibility of MG, and association of rs231775 and rs3087243 with the susceptibility of ocular onset MG, but no association with the severity of MG.

The cause of myasthenia gravis (MG) is unknown, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals. The human leukocyte antigen (HLA) region is considered to be the most important genetic region for MG susceptibility genes. To investigate the association between HLA-DRB1 and myasthenia gravis (MG) in a northern Han Chinese population, a polymerase chain reaction with sequence-specific oligonucleotide probe hybridization method was used to determine the HLA-DRB1 genotypes of 91 patients with MG and 171 healthy individuals. We found that the HLA-DRB1(*)09 allele was significantly more prevalent among patients with MG than among healthy controls, especially those who experienced early onset of the disease (≤40 years), those who were seronegative for acetylcholine receptor antibody, and those with ocular MG. The prevalence of the HLA-DRB1(*)08 allele was significantly lower among patients with MG than among controls. These results indicate that HLA-DRB1(*)09 might be positively associated and DRB1(*)08 negatively associated with MG in the northern Han Chinese population.