Association Between CTLA-4 Gene Polymorphisms And The Prognosis Of Ocular Myasthenia Gravis And Glucocorticoid Sensibility

Objective To explore the association between four SNPs(rs733618,rs5742909,rs231775 and rs3087243 in CTLA-4)polymorphisms and the conversion of ocular myasthenia gravis patients(OMG).To explore the association between four SNPs(rs733618,rs5742909,rs231775 and rs3087243 in CTLA-4)polymorphisms and the response to glucocorticoids in patients with myasthenia gravis(MG).Methods We genotyped four SNPs(rs733618,rs5742909,rs231775 and rs3087243 in CTLA-4)with SNPscan TM technique.According to the purpose of the study and the inclusion criteria,twe analysis sets were selected from 480 MG patients and 487 healthy controls.A total of 233 adult OMG patients were included in the study of the conversion of OMG.A total of 256 adult MG patients were included in the study of the response to glucocorticoids in MG patients.Differences of clinical features were compared between SGMG and OMG and between glucocorticoid insensitive subgroup and sensitive subgroup.The allele frequencies were compared between SGMG and the OMG,between glucocorticoid insensitive subgroup and sensitive subgroup and between glucocorticoid insensitive/sensitive subgroup and healthy controls.Genotype frequencies were compared under codominance model.Taking the conversion(SGMG/OMG-R)as dependent variable,the sex,age of onset,thymus condition,ACh R antibody status,and rs733618,rs231775,and rs3087243 genotype(under codominance model)as independent variable,binary logistic regression was used to search for independent risk factors of the conversion of OMG.Taking the glucocorticoid sensitivity as dependent variable,the sex,age of onset,onset muscle involvement,thymus condition,ACh R antibody status,course before glucocorticoid treatment,the score of QMG before glucocorticoid treatment and rs733618,rs231775,and rs3087243 genotype(under codominance model)as independent variable,binary logistic regression was used to search for independent risk factors of glucocorticoid sensitivity in MG patients.Results There were no significant differences in allele and genotype frequencies of rs733618,rs231775 and rs3087243 between SGMG and OMG.The percentage of patients with thymoma in SGMG were significant higher than that in OMG-R(P=0.002OR=2.899,95% CI 1.479~5.681).The percentage of ACh R-Ab positive patients in SGMG were significant higher than that in OMG-R(P=0.027 OR=1.949,95% CI1.084~3.502).Taking the conversion(SGMG/OMG-R)as dependent variable,the sex,age of onset,thymus condition,ACh R antibody status,and rs733618,rs231775,and rs3087243 genotype(under codominance model)as independent variable,binary logistic regression was used to find that thymoma is the independent risk factors of conversion of OMG(P=0.003).There were no significant differences in allele and genotype frequencies of rs733618,rs231775 and rs3087243 between MG glucocorticoid insensitive subgroup and MG glucocorticoid sensitive subgroup and between each of the two MG subgroups and healthy control.The percentage of patients began glucocorticoid treatment 6 months after disease onset in glucocorticoid insensitive subgroup were significant higher than that in glucocorticoid sensitive subgroup(P=0.03 OR=2.755 95%CI=1.138~6.670).Taking the glucocorticoid sensitivity as dependent variable,the sex,age of onset,onset muscle involvement,thymus condition,ACh R antibody status,course before glucocorticoid therapy,the score of QMG before glucocorticoid therapy and rs733618,rs231775,and rs3087243 genotype(under codominance model)as independent variable,binary logistic regression was used to find that started glucocorticoid therapy 6 months after onset of MG is independent risk factors of glucocorticoid sensitivity in MG patients(P=0.003).Conclusion No association were found between CTLA-4 gene polymorphisms and the conversion of ocular myasthenia gravis and glucocorticoid sensibility.Thymoma is the independent risk factors of conversion of OMG.Started glucocorticoid therapy 6months after onset of MG is independent risk factors of glucocorticoid sensitivity in MG patients.