Polymorphism In HLA-DQB1 And TNF-α And Genetic Susceptibility To Familial Myasthenia Gravis In North China

Objective To explore the relationship between the HLA-DQB1, TNF-(-1031T/C,-863C/A) gene polymorphisms and familial myasthenia gravis(MG) in north China.Methods The HLA-DQB1 and TNF-agene polymorphisms were determined by PCR-SSP and RFLP respectively in 64 MG patients(15 familial and 49 sporadic)and 52 healthy controls. The measurement data was analyzed statistically by t -test and enumeration data by chi-square test.Results (1) The frequency of DQB1*0501 was significantly increased in the familial MG compared with sporadic MG(P<0.05,OR=3.08) and healthy controls(P<0.01,OR=4.439), especially in the ocular form.(2) Compared with healthy controls, the frequency of DQB 1*0301/4 was increased (P<0.05, OR=2.56), while the frequency of DQB1*0601 was significantly decreased (P<0.05,OR=0.33) in sporadic MG, moreover these differences were statistically significant in the late-onset( 40) group, generalized form and without thymoma subgroup.(3)The frequency of DQB1*0604 was increased in the sporadic MG with thymomas (P=0.028, OR=3.345).(4) It was not found significance among familial MG, sporadic MG and healthy controls(P>0.05) in TNF-1031 T/C-863C/A . However, The TNF-1031 C allele was increased in the sporadic male MG(P<0.05) compared with healthy controls,and a positive association of the allele was observed in the sporadic MG with thymomas subgroup compared with that without thymoma (P<0.05).The frequency of TNF-1031 C allele was increased in the late-onset(>40) sporadic MG,but without statistically significance (P=0.091 , OR=2.063).Conclusions DQB 1*0501 allele is positively related to the genetic susceptibility of familial MG patients in north China especially in the ocular form. DQBl*0301/4 allele is positively related to the pathogenesis of sporadic MG. DQB 1*0601 maybe is a protecting allele for sporadic MG. DQB 1*0604 allele is associated with the spordic MG with thymomas. TNF-1031 C allele may predispose to the development of themale sporadic MG, especially in patients with thymomas. The phenotype of MG might be the result of interaction of hereditary factors. Familial MG might be different from sporadic patients in genetic immune mechanism. It may show the different genetic machanism between the MG with thymoma and that without thymoma.