The Association Between FOXP3 3279, IVS9+459 Polymorphisms And The Susceptibility Of Myasthenia Gravis

Background and objective:Myasthenia gravis (MG) is an autoimmune disease characterized by neuromuscular junction disorder, and its etiopathogenisis is not yet very clear. It is well known that MG is a complex disease, of which genetic, immue and environmental factors may influence the susceptibility to the disease.The FOXP3 gene is primarily expressed in CD4+CD25+ T-regs in normal physiological conditions.The protein coded by FOXP3 gene is vital for the development of regulatory T cells.It functions as a transcriptional repressor and down-regulates cytokines production in T cells.The polymorphism of FOXP3 gene may change FOXP3 functionally or quantitatively,therefore leading to the lack of functional CD4+CD25+ T-regs and autoimmune disorders.Since a significant decrease in the number and function of CD4+CD25+ T-regs could be observed in patients with MG. We hypothesized that the polymorphism of FOXP3 might be associated with the development of MG.This aim of this study is to evaluate the relationship between FOXP3-3279,IVS9+459 polymorphisms and susceptibility to myasthenia gravis.Methods:118 patients were collected from Xiangya Hospital during 2009-2010.All patients were diagnosed clinically and supported by laboratory test.Controls were obtained from 124 age-and sex-matched healthy individuals.FOXP3-3279 polymorphism were genotyped by the PCR sequence specific primer (PCR-SSP) technique.FOXP3 IVS9+459 polymorphism were genotyped by the PCR-RFLP technique.Results:1.The frequencies of FOXP3-3279 genotypes were AA 3.2%,AC 23.4%,CC 73.4%;the frequencies of A/C allele were A 14.9% and C 85.1%. The frequencies of FOXP3 IVS9+459 genotypes were AA 64.5%,AG 29.8% and GG 5.7%;the frequencies of A/G allele were A 79.4% and G 20.6%.2.FOXP3 IVS9+459 polymorphism revealed significantly differences of genotype and allele distribution between patients and controls (P<0.05). MG patients have a lower frequency of the G allele than controls (OR=0.464, 95%CI=0.260-0.829,P=0.009). FOXP3 IVS9+459 AG genotype was associated with a lower risk of MG in males (OR=0.098, 95%CI=0.012-0.796,P=0.008).There were no evidence indicated the association between FOXP3 IVS9+459 polymorphism and the onset age of MG.The GMG patients have a lower frequence of the G allele than controls(P=0.011,OR=0.472,95%CI= 0.262-0.853),while the OMG patients have a lower frequence of AG genotype compared to controls(P=0.003,OR=0.191,95%CI=0.055-0.657).There were no significant difference of FOXP3 IVS9+459 genotype and allele distribution among thymoma, thymic hyperplasia and thymus normal patients(P>0.05).3.FOXP3-3279 polymorphism revealed no significant difference of genotype and allele distribution in MG patients and controls.Moreover, no evidence indicated the interaction between FOXP3-3279 polymorphism and clinical characteristics of MG.4.Linkage disequilibrium was found between FOXP3-3279 and FOXP3 IVS9+459.But there were no significant difference of haplotypes distribution between the patients and controls.Conclusions:1.FOXP3 IVS9+459 polymorphism was associated with the susceptibility of MG in Han people of South China. It suggested that FOXP3 IVS9+459 G allele might be a protective genetic factor against MG.2.There were no significant association between FOXP3-3279 polymorphism and MG in Han people of South China.