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

Tumor necrosis factor-a-308 gene polymorphism affects the therapeutic efficacy of etanercept on ankylosing apondylitis

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50mg，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。

Objective ： To investigate the correlation between the efficacy of etanercept and tumor necrosis fac- tor-α-308 （TNF-α-308） gene polymorphism in patients with ankylosing apondylitis （AS）, and to study the poten-tial 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 pro- portion with BASDAI promotion between 20% - 50% among the three groups, there was significantly higher pro- portion 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.