The Association Study Beween X-linkd IRAK1 Gene Polymorphism And MRNA Expression And The Susceptibility To NMOSD

Objective:To investigate the relationship between the polymorphism of the immunoregulatory gene IRAK1 gene located on the X chromosome and the mRNA expression and the susceptibility to NMOSD。Methods:Using blood genomic DNA extraction kits,102 NMOSD patients and 213 healthy controls were used to extract DNA from peripheral blood,and Snapshot kits were used to perform 4 common loci of IRAK1-rs1059702、rs7061789、rs1059703、rs3027898 was analyzed,and the relative expression level of IRAK1mRNA was determined by q PCR technology in 30 patients with acute NMOSD and 15 healthy normal controls.Use SPSS software to perform Hardy Weinberg equilibrium test,IRAK1linkage disequilibrium（LD）pattern and haplotype analysis for the genotyping of selected female populations,and chi-square test for the association between base and genotype frequency and NMOSD susceptibility And logistic regression analysis。Results:1.Compared with the healthy female control group,the smallest allele G of rs1059702 showed a significantly lower frequency in NMOSD female patients（OR=0.486;P=0.006）,and G was a protective factor for NMOSD.Compared with healthy female controls,the risk of NMOSD for mutant homozygous GG genotype was lower than that for wild-type AA genotype（OR=0.203;P=0.011）.Moreover,this association was still statistically significant after adjustment for age(adjusted OR=0.238;P_corr=0.017).Similarly,rs7061789,rs1059703,and rs3027898 also showed significantly different allele and genotype distributions among NMOSD female patients compared with healthy controls.2.The frequency of this haplotype of AGGC is significantly higher in NMOSD female patients than in the normal female control group,and the difference is statistically significant（OR=1.892;P=0.017）.3.The gene types of the four IRAK1 SNPs have nothing to do with the female patients’AQP4-Ig G,the location of first symptoms,and the age of first onset.4.The expression of IRAK1 mRNA in the acute phase of NMOSD patients was significantly higher than that of the normal control group,and the difference was statistically significant.（P<0.001）.For rs1059703,Compared with heterozygous AG,homozygous GG of NMOSD in female acute stage,the expression of GG group was higher than that of AG group,and the difference was statistically significant.（P<0.05）.The mRNA expression level of AGGC risk haploid was significantly higher than that of non-risk haploid.Conclusions:1.IRAK1 gene polymorphism on X chromosome is associated with susceptibility to NMOSD.2.IRAK1 gene polymorphism may affect the susceptibility of NMOSD by affecting mRNA expression.