Correlation Analysis Between Autophagy-related IRGM Gene And Ankylosing Spondylitisin The Han Chinese

Objective: It is known that ankylosing spondylitis(AS)and inflammatory bowel disease(IBD)shared a common genetic component,and mounts of previous papers have shown that autophagy-related gene IRGM(Immunity-related GTPase Family M)confer susceptibility to IBD.The gist of current study is to assess the role of IBD-associated autophagy gene IRGMon AS susceptibility in a Chinese Han population.Methods: Among 1270 unrelated subjects enrolled in present study,643 AS patients were selected from the outpatientdepartment of the 1st Affiliated Hospital of Anhui Medical University,and all of them fulfill the diagnostic criteria for AS in 1984;as to controls,627 healthy people with matchedage,sex and ethnicity with AS cases were recruited from the Blood Center in Hefei,China.Two tag SNPs(rs10065172 and rs4958846)were selected and were genotyped by Improved Multi-Ligase Detection Reaction(i MLDR)Assay technology.Genotypes and alleles frequencies analysis were conducted by using SPSS 16.0 software,and then three genotypeswere conducted to compare the distributions of the 2 tag SNPs between AS group and control group.Linkage disequilibrium(LD)was performedand then haplotype analyses were further constructedbased on the results of LD in haploview 4.2 software to identify the relationship between IRGM and AS susceptibility.Haplotypes whose frequencies arenot greater than 0.03 among both cases and controls were enrolled in each analysis.In addition,we also investigated the relationship between genetic polymorphisms and clinical phenotypes(i.e.CRP,ESR,disease duration,BASDAI and BASFI)in AS group.Similar analyses were conducted for ten environmental actors.Subgroup analysis based on gender was also conducted for further information.Continuous data with normalized distribution were presented as mean±SD,and non-normalized continuous data were shown as median(IQR).All statistical tests were two sides and P<0.05 was considered to be statistically significant,unless corrected for multiple comparisons by Bonferroni correction.P-value for a truly significant result was calculated as 0.05/n.Results: The mean age of 643 AS patients(527 males and 116 females)was 28.2±8.9 years;as to control group(515 males and 112 females),the mean age was 27.8±7.6 years.No significant differences were identified between the two groups in term of age(t =-0.882,P=0.378)and gender(?2=0.007,P=0.934).HLA-B27 tests were positive in 93.6%of AS patients,and the mean disease duration,Erythrocyte sedimentation rate(ESR),C reactive protein(CRP),Bath AS Functional Index(BASFI)and Bath AS Disease Activity Index(BASDAI)were 2.8(0.5,6.0)years,11.0(2.0,25.0)mm/h,6.8(1.1,23.7)mg/L,0.9(0.0,2.4)cm and 1.8(0.4,3.3)cm,respectively.Both of thetag SNPs(rs10065172 and rs4958846)were in Hardy-Weinberg equilibrium(HWE)in control group(P=0.180 and P=0.893).The genotype and allelic frequencies of each tag SNP were compared between case and control groups,but no significant associations were identified(P>0.05 for both).In addition,through the stratified analysis based on gender,a slight association between rs4958846 and female patients with AS was detected concerning genotype and allele frequencies(?2= 6.049,P=0.049;?2= 4.626,P=0.031).However,neither of them was survived after Bonferroni correction(?=0.05/2 = 0.025).Logistic regression analysis revealed that carriers with CT+TT or CT genotype had a significantly decreased risk for developing AS among female subjects when compared with CC genotype(OR=0.514,95%CI0.301-0.876,P=0.014;OR=0.518,95%CI0.297-0.902,P=0.020,respectively).Additionally,a risk haplotype rs4958846C-rs10065172C(OR=2.093,95%CI1.301-3.368)and a protective haplotype rs4958846T-rs10065172C(OR=0.652,95%CI0.441-0.964)were also identified to be associated with female AS.There were none associations of the genotypes of each SNP withclinical phenotypes,and then subgroupanalysis also obtains the same results.As to ten environmental variables,only marginal association was found between daily vegetable intake and AS susceptibilityunder univariate logistic regression model(OR=4.895,95%CI1.011-23.709,P=0.048),while none significant relationship was identified under multivariate logistic regression model.Conclusions: Autophagy-associated IRGM gene is also associated with AS susceptibility in the Chinese female population,indicating that autophagy pathway may involve in AS genetic predisposition.