Association analysis between B cell activating factor gene polymorphisms and 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 were genotyped with SNPscan™ technique. A total of 480 patients with MG who were diagnosed and followed up from November 2007 to June 2013 in the Affiliated Hospital of Qingdao University and Beijing Friendship Hospital, Capital Medical University and 487 healthy people in the same district were enrolled in this study. The frequencies of alleles were compared among 487 healthy controls and 480 MG patients with different subgroups specified by gender, onset age, thymoma, AChRAb, 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 For rs3759465 and rs16972197, the frequencies of C allele were significantly higher in the generalized MG subgroup (103/536; 103/542) than that in the ocular MG subgroup (38/298, OR=1.628, 95% CI 1.088–2.434, χ2=5.698, P=0.017; 40/302, OR=1.537, 95% CI 1.034–2.283, χ2=4.570, P=0.033) and that in the control group (147/970, OR=1.332, 95% CI 1.009–1.758, χ2=4.114, P=0.043; 145/974, OR=1.341, 95% CI 1.016–1.771, χ2=4.313, P=0.038); there were statistically significant differences in genotype frequencies under codominant (P=0.015; P=0.036) and additive (P=0.014; P=0.028) inheritance models between the generalized MG subgroup and the ocular MG subgroup, as well as between the generalized MG subgroup and the control group under both codominant (P=0.029; P=0.024) and additive (P=0.045; P=0.041) inheritance models. Statistically significant differences were also found in genotype frequencies between the Oosterhuis 3–5 scores subgroup and the control group under the codominant inheritance model in both rs3759465 and rs16972197 (P=0.031; P=0.023), as well as between the Oosterhuis 0–2 and 3–5 scores subgroups in rs3759465 (P=0.047) under the codominant inheritance model. There were no statistically significant differences among the other comparisons. Conclusions BAFF gene rs3759465 and rs16972197 polymorphisms may be associated with the susceptibility of generalized MG subgroup and the severity of MG. There is no evidence to support the association between the polymorphisms of rs9514828, rs8181791, rs16972229, rs12428930, rs10508198 and rs3783117 and the susceptibility and severity of MG. Key words: Myasthenia gravis; B-cell activating factor; Polymorphism, single nucleotide; Genetic predisposition to disease; Severity of illness index