Association Research Of Inflammatorycytokin Signaling Related Genes Polymorphism With Ankylosing Spondylitis

Object Ankylosing spondylitis is an autoimmune, chronic in?ammatory disease. Studies have previously demonstrated that cytokine TNF-αand some other inflammatory cytokines are related to AS and yet A20 and IL-12 are related to TNF-α. Now the method of research based on pathway has become a new approach to find out disease candidate genes. The aim of the present study was to select 3 SNPs in A20 gene , and 15 SNPs within or nearby IL-12 pathway related genes IL12B,IL12RB2,JAK2,STAT3,STAT2,STAT4, then do a case-control association research and find out the new candidate gene.Method 18 SNPs were genotyped in 56 cases and 56 controls from Jilin population by HRM and PCR-FRLP, then replication was completed in Ningxia population with 298 cases and 339 controls.Results (1) Alleles frequencies of 17 SNPs except from rs 610604(P=0.031) in inflammatory signaled pathway were not associated with AS in Jilin population, all P values were >0.05 (2) Haplotypes analysis of chromatosome 5 : The haplotypes GAG of rs 17728338, rs 3212227 and rs 3213094 (P=0.02;OR=1.896,95% CI:1.102-3.264), GGA of rs 17728338,rs 6887695 and rs 3212227 (P=0.013;OR=2.016,95% CI:1.159-3.508), GA of rs 6887695 and rs 3212227 (P=0.03;OR=1.806,95% CI:1.056-3.090), AG of rs 3212227 and rs 3213094(P=0.023;OR=1.852,95% CI:1.088-3.152)were more common in AS than in control with significant differences. All of the four haplotypes, only wild allele A of rs 3212227 exited in all four haplotypes, which indicated that A might be a major allele that led to individuals susceptibility to AS in Jilin. (3) Haplotype analysis of A20: The haplotypes CTC of rs 5029939,rs 2230926 and rs 610604(P=0.039;OR=2.732,95% CI:1.019-7.323), CC of rs 5029939 and rs 610604 (P=0.039;OR=2.732,95% CI:1.019-7.323), TC of rs 2230926 and rs 610604 (P=0.025; OR=2.944,95% CI:1.107-7.830) were more common in AS than in control with significent differences. All of the there haplotypes, only wild allele C of rs 610604 exited in all there haplotypes, which indicaded that C might be a major allele that led to individuals susceptibility to AS in Jilin. (4) CC genotype of rs 610604 was associated with AS (2.68% vs 0.59%,P1/2=0.034) in Ningxia group and still in a combinated group (Pjiont =0.037). Conclusion (1) The haplotype of rs 3212227,rs 3213094,rs 6887695 of IL12B and rs 17728338 in chromatosome 5 or nearby the haplotype in inflammatory signal pathway might be associated with AS. Wild allele A of rs 3212227 consistenly exited in all four haplotypes, which indicaded that A might be a major allele that led to individuals susceptibility to AS in Jilin. (2) The haplotype of rs 5029939,rs 2230926,rs 610604of A20 or nearby the haplotype in inflammatory signal pathway might be associated with AS. Wild allele C of rs 610604 consistenly exited in all four haplotypes, which indicaded that A might be a major allele that led to individuals susceptibility to AS in Jilin. (3) Analysis for the conmbination group showed that CC genotype frequency of rs 610604 might be associated with AS (Pjiont =0.037).