强直性脊柱炎患者TNF-α-308位点基因多态性对依那西普疗效的影响

摘要

Objective： To investigate the correlation between the efficacy of etanercept and tumor necrosis factor-α-308 (TNF-α-308) gene polymorphism in patients with ankylosing apondylitis (AS) , and to study the potential mechanism.Methods: One hundred patients with AS were genotyped by polymerase chain reaction for TNF-α-308 gene polymorphism and given with etanercept (50 mg, hypodermic injection, once a week for 12 weeks).Clinical therapeutic efficacy was assessed according to Bath ankylosing spondylitis activity index ( BASDAI) and Assessment in ankylosing spondylitis (ASAS) after 12 weeks.Results: Significantly lower proportion of patients with BASDAI promotion lower than 20％ was observed in G/G group, comparing with those in G/A and A/A groups (9％ vs 40％ and 9％ vs 50％ , respectively, P ＜0.05).Although no significant difference in patients proportion with BASDAI promotion between 20％ ～ 50％ among the three groups, there was significantly higher proportion of patients with BASDAI promotion greater than 50％ in G/G group, comparing with those in G/A and A/ A groups (63％ vs 20％ and 63％ vs 25％ , respectively, P ＜0.05).Significantly greater proportion of patients in G/G group reached ASAS20 was revealed, comparing with those in G/A and A/A groups (94％ vs 70％ and 94％ vs 75 ％ , respectively, P ＜ 0.05 ).However, there was no significant difference in proportion of patients reached ASAS50 and ASAS70 among the three groups.Conclusion: The data suggested that the therapeutic efficacy of etanercept on AS in patients with TNF-α-308 G/G genotype is better than those with G/A and A/A genotypes, suggesting genotyping of TNF-α-308 is a prediction factor in etanercept treatment of AS patients.%目的:研究AS患者TNF-α-308位点基因多态性与依那西普疗效的关系,初步探讨TNF-α-308位点基因多态性对分子靶向治疗的影响机制.方法:100例已作TNF-α-308位点基因分型的AS患者分为G/G组(86例)、G/A组(10例)、A/A组(4例),给予依那西普治疗(用法:第1~12周,每次50 mg,每周1次皮下注射),12周后以BASDAI评分、ASAS评估AS患者对依那西普分子靶向治疗的效果.结果:与依那西普治疗前比较,给予依那西普治疗12周后,G/G型AS 患者BASDAI评分改善少于20%的比例显著低于G/A型(9%对比40%,P＜0.05)和A/A型(9%对比50%,P＜0.05),各组间BASDAI评分改善20%~50%的比例比较差异无统计学意义(P＞0.05);G/G型BASDAI评分改善超过50%的比例显著高于G/A型(63%对比20%,P＜0.05)和A/A型(63%对比25%,P＜0.05),G/G型达到ASAS20的比例显著高于G/A型(94%对比70%,P＜0.05)和A/A型(94%对比75%,P＜0.05);G/G型、G/A型、A/A型分别达到ASAS50、ASAS70的比例比较差异无统计学意义(52%对比40%对比25%;24%对比30%对比25%,P＞0.05).结论:TNF-α-308位点基因多态性对依那西普靶向治疗的效果可能有一定的影响,G/G型患者的治疗效果要优于G/A型和G/G型,该位点基因分型可能可以作为依那西普治疗AS效果的预测工具.