Susceptibility Analysis Between The Single Nucleotide Polymorphism Of TRAF2 And TRAF5 Gene And Ankylosing Spondylitis

Objective:To investigate the role and interaction of eight locus polymorphisms of TRAF2 and TRAF5 genes and the susceptibility and disease activity of ankylosing spondylitis.Methods:A total of 1360 subjects were enrolled in this study,patients with AS from the Department of Rheumatism and Immunity of the First Affiliated Hospital of Anhui Medical University were 673.The healthy controls totaling 687 were matched according to the frequency of gender and age.They were from the medical examination center of the First Affiliated Hospital and the blood station of Hefei City.Eight SNPs(rs3750511,rs10781522,rs17250673,rs59471504,rs6540679,rs12569232,rs4951523,rs7514863)were selected and were genotyped by SNPscan Assay technology.Allele frequencies and genotypes analysis were conducted.The distribution of SNP genotypes in different gender and disease function index were analyzed,and the association between genotypes and allele frequencies of TRAF2 and TRAF5 in AS patients with different HLA-B27 status was analyzed.The interaction between genes and between gene and environmental factors were analyzed.SPSS 16.0 software was used for statistical analysis.Qualitative data were expressed by frequency(%)and intergroup analysis was performed by?~2test.Quantitative data of normal distribution were expressed by Mean±SD,and t test was used for comparison between two groups,while quantitative data of non-normal distribution were expressed by Median(IQR),and Mann-Whitney U test was used for comparison between two groups.The test level was set at 0.05 on two-sides.Bonferroni method was used to correct the multiple comparisons.Results:The mean age of 673 AS patients(548 males and 125 females)was(28.62±7.76)years.The mean age of control group(560 males and 127 females)was(28.58±9.31)years.No significant differences were identified between the two groups in term of age(t=0.087,P=0.931)and gender(?~2=0.002,P=0.967).Positive rate of HLA-B27 tests were 61.9%of AS patients,and the mean disease duration,Bath Ankylosing Spondylitis Functional Index(BASFI),Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)and Ankylosing Spondylitis Disease Activity Scores(ASDAS-CRP)were 2(0.6,3.8),0.9(0,2.6)and 3.28(2.58,4),respectively.All of the SNPs were in Hardy-Weinberg equilibrium(HWE)in control group.The allelic frequencies and genotype of each SNP were compared between case and control groups,but no significant associations were identified,P>0.05 for all.In addition,through the stratified analysis based on gender,a slight association between rs3750511 and female patients with AS was detected concerning genotype(?~2=5.907,P=0.033).However,it was not survived after Bonferroni correction(?=0.05/2=0.025).There was significant association of the genotypes of rs10781522 between BASDAI<4 and BASDAI?4 in the AS patients(?~2=4.434,P=0.035).However,it was not survived after Bonferroni correction(?=0.05/2=0.025).There was significant association of the genotypes of rs3750511 between BASDAI<4 and BASDAI?4 in the AS patients(?~2=10.962,P=0.004)and it was survived after Bonferroni correction(?=0.05/2=0.025).Cross-validation consistency and the prediction error obtained from MDR analysis for each number of loci were calculated.One three-locus model TRAF2(rs10781522,rs17250673)and TRAF5(rs12569232)had a maximum testing accuracy of 52.67%and a maximum cross-validation consistency(10/10)that was significant at the level of P=0.0001,after determined empirically by permutation testing.As to ten environmental variables,only marginal association was found between sleep quality and AS susceptibility by univariate logistic regression model while none significant relationship was identified under multivariate logistic regression model.Conclusions:In summary,our results indicate that the SNPs of TRAF2 and TRAF5does indicate a correlation with the development of ankylosing spondylitis in the Han population,but the genotype frequency of rs3750511 locus is associated with ankylosing spondylitis after gender stratification.We found that two loci rs10781522and rs375051 were related to genotype frequency distribution or allele frequency distribution was association with ankylosing spondylitis.Our results also showed that there were significant correlations between TRAF2(rs10781522,rs17250673)and TRAF5(rs4951523)and ankylosing spondylitis in gene-gene interaction model.