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Objective Recent studies have shown that ORMDL3 at 17q21 is associated with Crohns disease (CD).Because ankylosing spondylitis(AS)and CD overlap in clinical and immune phenotypes,ORMDL3 may also contribute to the development of AS.The aim of this study was to test whether ORMDL3 and 17q21 variants are associated with the susceptibility to AS in Chinese population.Methods To search for novel variants,we sequenced all exons including UTR and the 1kb upstream regulatory region of ORMDL3 gene.However,we did not frnd any non-Hap-Map SNPs in these regions.Seven SNPs:rs7216389,rs12603332,rs12936231,rs9303277,rs11557467,rs1007654,and rs17608925,which were selected from chromosome 17q21 containing ORMDL3,GSDMB,ZPBP2,IKZF3 gene,were genotyped by Taqman SNP genotyping assay.Results A total of 753(557 males,73.97%)unrelated AS patients and 1120(792 males,70.71%)ethnically matched healthy controls were recruited.All patients,met the modified New York criteria,and had no history of Inflammatory Bowl disease and/or psoriasis.Radiographic severity of AS was graded by CT on a scale of 1-4 (for suspicious,mild,moderate,and severe).And 30 cases were ascertained as grade 1 (Suspicious),222 of them were grade 2(Sclerosis,some erosions),384 of them belonged to grade 3(Severe erosions,widening of the joint space,some ankylosis),and 72 of them belonged to grade 4(Complete ankylosis).And five of the SNPs:rs7216389,rs12603332,rs12936231,rs9303277 and rs11557467 were associated with AS,all P≤0.01,especially in males,all P<0.00001,even after Bonferroni correction(rs7216389,OR 0.83,95%CI 0.715-0.954,P=0.01,ORm 0.71,95%CI 0.595-0.842,Pm=4.41E-05,aPm=3.09E-04;rs12603332,OR 0.82,95%CI 0.711-0.946,P =0.007,ORm 0.71,95%CI 0.596-0.841,Pm=8.15E-05,aPm=5.71E-04;rs12936231,OR 0.82,95%CI 0.708-0.946,P=0.007,ORm 0.69,95%CI 0.580-0.822,Pm=2.97E-05,aPm=2.08E-04;rs9303277,OR 0.83,95%CI 0.721-0.956,P=0.01,ORm 0.71,95%CI 0.603-0.845,Pm=4.15E-05,aPm=2.91E-04;rs11557467,OR 0.80,95%CI 0.695-0.930,P=0.003,ORm 0.70,95%CI 0.584-0.827,Pm=4.79E-05,aPm=3.35E-04).Besides,rs7216389,rs12603332,rs12936231 and rs11557467 were strikingly associated with severity of the disease based on radiographic findings(P<0.05),and rs11557467 had a marginal p value(OR 0.810,95%CI 0.687-0.955,P=0.012,ORm 0.779,95%CI 0.653-0.929,Pm=0.005).In addition,a specific haplotype TCCCGAT significantly increased the risk of AS,especially in males(OR 1.317,95%CI 1.073-1.616,P=0.008,ORm 1.411,95% CI 1.110-1.794,Pm=0.005),over the haplotype TCCCGGT.Conclusions Our study confirmed that variants in chromosome 17q21 were significantly associated with AS in a Chinese Han population,especially in males.Moreover,we demonstrated for the first time that the variants in this region were linked to the severity of this disease.