Association Of BAFF Gene Polymorphism With Myasthenia Gravis

Objective To explore the association between polymorphisms of B cell activating factor(BAFF) gene and the susceptibility and severity of myasthenia gravis(MG).Methods Eight SNPs(rs10508198, rs12428930, rs16972197, rs3759465, rs9514828, rs3783117, rs16972229 and rs8181791) in BAFF gene was genotyped with SNPscanTM technique. The frequencies of alleles were compared among 487 healthy controls and 480 MG patients with different subgroups specified by gender,onset age, thymoma, ACh RAb, muscle involvement at onset, maximal muscle involvement and maximal Oosterhuis score during two years after onset of MG. Genotype frequencies were compared under the codominant and log-additive modes of inheritance.Results In rs3759465 and rs16972197, the frequencies of C allele were significantly higher in generalized group than in ocular group(P=0.017, OR=1.628, 95%CI 1.088-2.434; P=0.033, OR=1.537, 95% CI 1.034-2.283) and in control group(P=0.043, OR=1.332, 95% CI 1.009-1.758; P=0.038, OR=1.341, 95% CI 1.016-1.771); there were significant differences in genotype frequencies under codominant(P=0.015, P=0.036) and additive inheritance(P=0.014, P=0.028) models between generalized MG and ocular MG subgroups, as well as between generalized MG subgroups and control group(Pcodominant =0.029, Padditive=0.024; Pcodominant=0.045, Padditive=0.041). Significant differences were also found in genotype frequencies between Oosterhuis 3-5 score subgroup and control group under the codominant inheritance model in rs3759465 and rs16972197(P=0.031, P=0.023), as well as between Oosterhuis 0-2 and 3-5 score subgroups in rs3759465(P=0.047)under the codominant inheritance model. There were no differences among the rest comparisons. After logistic regression, severity was found to be related with Ach RAb while genotypes were not independent risk factors for severity.Conclusions BAFF gene rs3759465 and rs16972197 polymorphisms may be associated with the susceptibility of generalized MG subgroup, and their association with the severity of MG was influenced by confounding factors which indicates that polymorphisms are not independent risk factors for disease’s severity. There are no evidence to support the association between the polymorphisms of rs9514828, 181791, rs16972229, rs12428930, rs10508198 and rs3783117 and the susceptibility and severity of MG.