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雌激素受体α基因多态性对熊去氧胆酸治疗原发性胆汁性肝硬化疗效的影响

Study on the effects of estrogen receptor alpha gene polymorphism on the efficacy of ursodeoxycholic acid in primary biliary cirrhosis treatment

摘要:

目的 探讨雌激素受体α(ERα)基因多态性对熊去氧胆酸(UDCA)治疗女性原发性胆汁性肝硬化(PBC)疗效的影响.方法 采用聚合酶链反应-限制性片段长度多态性方法 检测65例女性PBC患者ERα基因1号内含子PvuⅡ和XbaⅠ酶切位点多态性.患者每日均予UDCA(13~15 mg/kg,分3次口服)治疗.随访患者临床症状和血清总胆红素(TBil)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)变化情况,共随访24个月.结果 共60例患者获完整随访资料.XX和PP型患者4项指标均缓慢下降,但至随访结束时未达治疗有效标准.Xx型患者4项指标亦缓慢下降,至随访结束时达治疗有效标准.Pp、pp、xx型患者4项指标均快速下降至治疗有效标准.UDCA治疗PBC有效率75%(45/60).PP、Pp、pp型患者和XX、Xx、xx型患者在UDCA治疗有效组和无效组中的分布差异均有统计学意义(x2=12.13、P=0.003和x2=9.95、P=0.007).Pp、pp、Xx、xx型患者有效率[分别为82.61%(19/23)、80.65%(25/31)、9/14、83.33%(35/42)]高于PP、XX型者(分别为1/6和1/4).结论 PBC患者ERα基因多态性影响UDCA的疗效.

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Objective To investigate the effects of estrogen receptor alpha (Erα) gene polymorphism on the efficacy of ursodeoxycholic acid (UDCA) in female primary biliary cirrhosis (PBC) treatment. Methods The polymorphism of Xba Ⅰ and Pvu Ⅱ sites in No. 1 Intron of Erαgene was detected by polymerase chain reaction-restriction fragment length polymorphism in 65 female patients with PBC. The patients were treated with UDCA tablets daily (13-15 mg·kg-1 · d- 1,divided for 3 times oral taking). The variations of patients' serum total bilirubin (Tbil), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyle transpeptidase (GGT) were followed up totally for 24 months. Results Totally the complete follow-up data had been obtained in 60 patients. Four indicators of XX or PP type patients slowly declined till the end of follow-up point still had not reached the effective treatment standard. Four indicators of Xx type patients were also slowly declined, while the effective treatment standard was achieved till the end of follow-up. Four indicators of Pp/pp or xx type patients were rapid declined to the effective treatment standard. The effective rate of UDCA in PBC treatment was 75.0% (45/60). The distribution difference of Pvu Ⅱ between the UDCA treating effective group and the ineffective group in PP, Pp, pp types patients and XX、Xx、xx types patients was statistic significant (x2 = 12.13、 P = 0.003 and x2 = 9.95 、 P = 0.007 respectively). The distribution difference of Xba Ⅰ between the effective group and the ineffective group with UDCA treatment in XX, Xx and xx types patients was also significant (P <0.05). The effective rate of Pp, pp, Xx, xx types patients [82.61% (19/23)、80.65% (25/31) 、9/14、83. 33% (35/42) respectively] was higher than PP and XX types patients (1/6 and 1/4 respectively).Conclusion Erα gene polymorphism influenced the efficacy of ursodeoxycholic acid in treating primary biliary cirrhosis.

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