Association Analysis Between IL-4R Gene Polymorphism And Myasthenia Gravis

Objective:To evaluate the impact of the polymorphisms within interleukin 4 receptor gene（rs1805010,rs1805011,rs1805015,rs1801275,rs2107356,rs8832）on the susceptibility to and severity of myasthenia gravis（MG）and the contribution to subtypes of MG.Methods:Six SNPs in IL-4R gene was genetyped by SNPsanTM.The frequencies of alleles and genetypes were compared among 480 MG patients and 487 healthy controls（HC）with different subgroups specified by gender,onset age（<15y/o,15-50y/o,>50y/o）,thymoma（+/-）,AChR-Ab（+/-）,muscle involvement at onset（ocular/generalized）and maximal Oosterhuis score in two years after the onset of the disease.The online SNPstats software（http://bioinfo.iconcologia.net/snpstats/start.htm）was used to test the Hardy-Weinberg equilibrium（HWE）in HC.c² test and Fisher exact test（SPSS 19.0）were used to compare allele frequencies（Bonferroni correction of the p value was used for adjusting multiple tests）.SNPstats was used to compare genotype frequencies under codominant genetic model between MG group and HC,each subgroup and HC,as well as each pairs of MG subgroups.When there were significant differences in frequencies of alleles between MG subgroups and HC or among MG subgroups,logistic regression was used to adjust the potential confounders under codominant genetic model.Haploview were applied to calculate pairwise linkage disequilibrium（LD）of SNPs.Results:No significant differences was suggested in the frequencies of alleles(after correction for multiple testing,P_Bon>0.05)or genotypes（P>0.05）between MG group and control group.Significant differences was found in allele frequencies between thymoma（+）subgroup and control group in rs1805010(P=0.002,OR=1.596,95%CI 1.180-2.158,P_Bon=0.012)and rs2107356(P=0.002,OR=1.627,95%CI 1.188-2.229,P_Bon=0.018).Significant differences was found in allele frequencies between thymoma（+）subgroup and thymoma（-）subgroup in rs1805010(P=0.001,OR=1.687,95%CI 1.236-2.302,P_Bon=0.006)and rs2107356(P=0.002,OR=1.627,95%CI 1.188-2.229,P_Bon=0.012).Under codominant genetic model,significant differences were found in genotype frequencies of rs1805010（P=0.008）and rs2107356（P=0.017）between thymoma（+）subgroup and HC;significant differences were found in genotype frequencies of rs1805010（P=0.004）and rs2107356（P=0.0025）between thymoma（+）and thymoma（-）subgroups.Frequency of rs1801275 G allele was significantly higher in AChR-Ab（+）subgroup than that in control group(P=0.003,OR=1.482,95%CI 1.146-1.915,P_Bon=0.018).Under codominant genetic model,significant difference was found in genotype frequencies of rs1801275 between AChR-Ab（+）subgroup and HC（P=0.0032）.Conclusion:rs1805010 and rs2107356 of IL-4R gene seems to be associated with an increased risk of thymoma in Chinese Han MG patients;rs1801275 seems to be associated with an increased risk of positive AChR-Ab in Chinese Han MG patients.The selected SNPs did not show any significant associations with the susceptibility to MG or severity of MG.