Association of tumor necrosis factor-α receptor gene single nucleotide polymorphism in patients with ankylosing spondylitis / 中华风湿病学杂志

ABSTRACT

Objective To investigate the value of tumor necrosis factor (TNF)-α receptor gene,TNFRSF1A+36A/G(rs767455) and-383A/C(rs2234649),TNFRSF1B+196T/G(rs1061622) single nucleotide polymorphism (SNP) for the susceptibility to ankylosing spondylitis (AS) and the relationship between SNP and AS.T test,Chi-square test,and ANOVA were used for statististical analysis.Methods Two hundred and fifteen patients who had definite diagnosis of AS and 216 healthy blood donors were involved in this study.SNPs of TNF-α receptor geneTNFRSF1A +36A/G(rs767455),-383A/C(rs2234649) and TNFRSF1B+196T/G (rs1061622) were detected with the ligase detection reaction (LDR-PCR) method.Results ① Distribution frequencies of A alleles(86.8％,91.5％) and G alleles (13.2％,8.5％) of TNFRSF1A(rs767455) in AS and controls were significantly different with each other (x2=4.627,P=0.0315),while the distribution frequency in group of homozygotes (AA or GG genotype) in AS and controls were 74.6％(150/201) and 83.9％(177/211),the frequencies in group of heterozygotes (AG) were 25.4％ (51/201) and 16.1％(34/211)(x2=5.390,P=0.020).Frequency of alleles and the genotypes of TNFRSF1A (rs2234649) and TNFRSF1B (rs1061622) between AS and control group were similar(P＞0.05).It also demonstrated that TNF-αreceptor gene haplotype (rs1061622T-rs2234649A-rs767455G) carriers apparently increased the susceptibility to AS (11.5％ vs 6.9％)(OR1.753,95％CI1.078～2.852,P=0.022).② Analysis of variance found that the duration of morning stiffness (F=3.168,P=0.044) and peripheral joint tenderness counts (F=4.598,P=0.011) among the three genotype groups of TNFRSF1B (rs1061622) in patient with AS were evidently differed with each other.Bath AS functional index (BASFI) among different genotype groups of TNFRSF1A (rs2234649) in AS had remarkable diversity (F=5.783,P=0.004).None of above indicators among groups of different genotypes of TNFRSF1A (rs767455) in AS were uniform (P＞0.05).③ Forty-four patients were treated with TNF-α antagonist (entanercept),25 mg,subcutaneous injection,twice weekly for 3 months,then followed with Sulfaslazine (SASP) 2.0 g/d and Celecoxib 0.4 g/d for another 9 months.ASAS20 was the primary endpoint for the evaluation of therapeutic effect at the visit of 3 month and 12 month.No associations were found between SNP and short or long term outcome of treatment with TNF-α antagonist in AS (P＞0.05).Conclusion TNFRSF1A (rs767455) SNP correlates with susceptibility to AS in Anhui Han local patients.Carriers of TNF-α receptor gene haplotype (rs1061622T-rs2234649A-rs767455G) may increase the susceptibility to AS.SNP of TNFRSF1B (rs1061622) is associated with disease activity in AS,while SNP of TNFRSF1A(rs2234649)relates to functional index of the disease.There is no association between SNP of TNFRSF1A / TNFRSF1B and short or long term outcome of treatment with TNF-α antagonist in AS.