| BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory joint disease whichcharacterized by sacroiliitis and axial joint inflammation,the ordinary clinicalmanifestations of AS are the spine and/or peripheral arthritis, severe cases can lead tohip or knee and other joint deformities or spinal stiffness and disability. Generallyincreasing of cytokine levels, predominantly tumor necrosis factor (TNF)-α, present inmost of cases. After binding to TNF-α receptor (TNFR), TNF-α could trigger a series ofinflammatory reactions, eventually result in disease progression and bone erosion inpatients with AS. This mechanism is considered as the mainly but not entirely cause ofphysical disability in AS. Some kind of modification of TNF-α or TNF-α receptor mayinfluence the occurrence and progress of disease, With recent development of moleculargenetics, studies about TNF-α receptor gene single nucleotide polymorphism(SNP) inAS get more and more attention lately.ObjectiveTo investigate the value of TNF-α receptor gene, TNFRSF1A+36A/G(rs767455) and-383A/C(rs2234649),TNFRSF1B+196T/G(rs1061622) SNP for the susceptibility to ASand the relationship between SNP and disease status of AS. Roles of TNFRSF1A/TNFRSF1B SNPs in prophesying short term and long term outcome of treatment withTNF-α antagonist in AS were explored simultaneously. Methods215patients who were definite diagnosed as AS and216healthy blood donors wereinvolved in this study. SNPs of TNF-α receptor gene: TNFRSF1A+36A/G(rs767455),-383A/C(rs2234649) and TNFRSF1B+196T/G(rs1061622) weredetected with the ligase detection reaction (LDR-PCR) method. Analyses of thedistribution frequency of alleles, genotype and haplotype in AS and control groups wereconducted Differences in clinical phenotype and efficiency of therapy with TNF-αantagonist were compared with each group of genotypes in AS.Result1. Distribution frequencies of A alleles(86.8%,91.5%) and G alleles (13.2%,8.5%) ofTNFRSF1A(rs767455) in AS and control significantly varied with each other(x2=4.627, P=0.0315), while the genotype frequencies which represented as AA (74.1%,83.4%), AG(25.4%,16.1%), GG(0.5%,0.5%) between the two groups had nodifference(P>0.05). Given the number of GG genotype in AS and control group wasonly one, respectively., we combined group of GG genotype with group of AAgenotype. After reanalysis, results showed that distribution frequency in new group ofhomozygotes(AA or GG genotype) in AS and control were74.6%(150/201) and83.9%(177/211), frequencies in group of heterozygote(AG) were25.4%(51/201) and16.1%(34/211). Difference between the two groups had statisticallsignificance(x2=5.390, P=0.020). Findings of TNFRSF1A(rs2234649) andTNFRSF1B(rs1061622) SNP indicated that frequency of alleles and the genotypebetween AS and control group were similar(P>0.05). It also demonstrated TNF-αreceptor gene haplotype (rs1061622T-rs2234649A-rs767455G) carriers apparentlyaugmented susceptibility to AS (11.5%vs6.9%)(OR:1.753,95%CI:1.078-2.852,P=0.022).2．Analysis of variance found: Duration of morning stiffness(F=3.168, P=0.044) andperipheral joint tenderness number(F=4.598, P=0.011) among three genotype groups of TNFRSF1B(rs1061622) in patient with AS obviously differed with each other,patients in group of TG genotype had the hightest values. Bath AS Functional Index(BASFI) among different genotype groups of TNFRSF1A(rs2234649) in AS hadremarkable diversity(F=5.783, P=0.004). There were no significant difference of anyother indicators, such as joint function, Bath AS disease activity index(BASDAI),thoracic expansion, schober test, erythrocyte sedimentation rate, C-reactive protein,positive rate of HLA-B27and X-ray stage of sacroiliitis among different genotypegroups of TNFRSF1A(rs2234649) and TNFRSF1B(rs1061622) in AS(P>0.05).None of above indicators among groups of different genotypes ofTNFRSF1A(rs767455) in AS were uniform(P>0.05).3.44patients were treated with TNF-α antagonist(etanercept) for3month,25mg,subcutaneous injection, twice weekly, followed with Sulfaslazine（SASP）2.0g/d andCelecoxib0.4g/d for another9month. ASAS20was the primary endpoint for theevaluation of therapeutic effect at the visit of3month and12month. No associationswere found between SNP and short or long term outcome of treatment with TNF-αantagonist in AS (P>0.05).Conclusion1. TNFRSF1A(rs767455) SNP correlates with susceptibility to AS in population ofAnhuiHannationality.CarriersofTNF-αreceptorgenehaplotype(rs1061622T-rs2234649A-rs767455G) may increase susceptibility to AS.2. SNP of TNFRSF1B(rs1061622) is associated with the disease activity in AS, whileSNP of TNFRSF1A(rs2234649) relate to functional index of the disease.3. There is no associations between SNP of TNFRSF1A/TNFRSF1B and short or longterm outcome of treatment with TNF-α antagonist in AS. |
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