The Research Of Relationship Between PTPN22,CTLA-4 Singe Nucleotide Polymorphsims And Thymoma Associated With Myasthenia Gravis

Objective To evaluate the association of PTPN22 and CTLA-4 gene single nucleotide polymorphism with the myasthenia gravis associated with thymoma in Chinese people located in Tianjin and to analyze the relationship between SNP of PTPN22 gene and SNP of CTLA-4 gene. So as to explore the pathogenesis of myasthenia gravis associated with thymoma.Methods 50 patients with thymoma, which include 40 patients associated with myasthenia gravis, and 50 healthy people as controls were investigated. PTPN22 gene polymorphism+1858C>T and CTLA-4 gene polymorphism 49A>G were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PTPN22 gene polymorphism -1123G>C at promoter was genotyped by single allele-specific primer polymerase chain reaction (SASP-PCR).Result1.+1858C>T singe nucleotidepolymorphism for PTPN22 gene was not exist in thepatients and controls (P>0.05)2. Statistic differences in alleles and genotype frequency of -1123G>C were observed between MG(+)-thymoma and controls (P=0.001 P=0.013), but The alleles and genotype frequency were not observed between MG(-)-thymoma&MG-thymoma(-) and controls (P=0.192,P=0.214 and P=0.067,P=0.254).3. Statistic differences in alleles and genotype frequency of 49A>G for CTLA-4 were observed between MG(+)-thymoma and controls (P=0.0000,P=0.003), but The alleles and genotype frequency were not observed between MG(-)-thymoma&MG-thymoma(-) and controls (P=0.077,P=0.261 and P=0.058,P=0.058).4. Individuals with PTPN22 CC genotype and CTLA-4 G alletes had an increased risk of developing paraneoplastic myasthenia gravis (OR=4.722, 95% CI: 1.460-15.277) compared with those with PTPN22 G allete and CTLA-4 AA genotype.Conclusion1. We not discovered the +1858C>T singe nucleotide polymorphism for PTPN22 gene, so we believe there are no mutation of this gene site in Chinese people in TianJin and no association between the thymoma-MG(+) and PTPN22+1858C>T SNP.2. Allele frequency of PTPN22-1123 with site C is higher than the normal group,but it is no significant difference between the others(the groups of the thymoma-MG (-), MG-thymoma (-) and normal group).It is suggested that comparing with genotype GG and GC, the genotype CC with mutant allcles with site C increases the risk of thymoma-MG (+) (OR=4.253,95%CI 1.565-11.556)3. In the group of thymoma-MG (+), Allele frequency of CTLA-4 gene 49A> G is significant higher than the control group, while the groups of the thymoma-MG (-) and MG-thymoma (-) have no statistical difference. It is suggested that in the CTLA-4 49A> G SNP, the variant GG genotype increases the risk of thymoma-MG (+) (OR=12.600,95%CI 1.526-104.035)4. There is a synergistic effect between CTLA-4 49A>G SNP and the PTPN22-1123G>C SNP in the susceptibility of increasing the thymoma-MG (+).Carrying the AG or GG genotype of CTLA-4 and the CC of PTPN22 with the genotype of CC are prone to getting a thymoma-MG(+).5. Single nucleotide polymorphisms of PTPN22 and CTLA-4 is related to the pathogenesis of thymoma-MG(+), which is expected to the monoclonal antibodies, which will provide a good potential application of single nucleotide polymorphisms of PTPN22 and CTLA-4,and a new direction of prevention and clinical treatment of thymoma-MG(+).