Association between CTLA-4 gene polymorphism and myasthenia gravis in a Chinese cohort.

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 rs733618C 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 rs231775A allele is significantly lower in ocular onset subgroup than in control group, and the frequencies of rs231775A allele and rs3087243A 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 rs231775A 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 rs733618C, rs231775G and rs3087243G 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.