多巴胺D_3受体基因Ser9Gly多态性与阿立哌唑及利培酮治疗效应的关联研究

An study on the association of DRD_3 gene Ser9Gly polymorphism with therapeutic effects of aripiprazole and risperidone

目的比较阿立哌唑与利培酮治疗女性首发精神分裂症患者的疗效和血浆催乳素水平变化及其与多巴胺D3受体(DRD3)基因Ser9Gly(rs6280)多态性的关联。方法选择完成8周阿立哌唑或利培酮治疗的女性首发精神分裂症患者各60例,于治疗前和治疗8周后分别评测阳性与阴性症状量表(positive and negativesymptom scale,PANSS)。采用放射免疫法检测血浆催乳素水平,DNA测序技术检测DRD3基因Ser9Gly多态性,分析DRD3基因Ser9Gly多态性与两药疗效及血浆催乳素变化的关联。结果治疗8周后,两组PANSS减分率的差异无统计学意义[(59.79±23.48)vs.(63.30±22.66),P>0.05],但利培酮组血浆催乳素的变化值高于阿立哌唑组[(26.92±9.48)vs.(-25.25±8.07),P<0.05]。利培酮组中C等位基因携带者的血浆催乳素的增加明显高于未携带者[(52.48±27.01)ng/mL vs(36.07±17.46),P<0.05];而阿立哌唑组中未见此差异[(-23.27±8.36)vs.TT(-26.05±8.11),P>0.05]。两组8周后PANSS减分率(%)与DRD3基因Ser9Gly的差异均无统计学意义:阿立哌唑组[CC+CT(57.83±19.94)vs.TT(56.84±18.46),P>0.05];利培酮组[CC+CT(53.94±21.08)vs.TT(60.38±19.37),P>0.05]。结论阿立哌唑治疗女性首发精神分裂症疗效与利培酮相当,但引起血浆催乳素水平变化的幅度较小;利培酮引起血浆催乳素水平增加可能与DRD3基因Ser9Gly多态性有关联。

Objectives To evaluate the efficacy and safety of aripiprazole or risperidone and their influences on plasma prolaetin （PRL） levels in female patients with schizophrenia at firs-onset stage. To explore the association of dopamine receptor D3 （DRD3） gene Ser9Gly poiymorphism with therapeutic and side effects of aripiprazole and risperidone. Methods One-hundred and twenty female patients with first-onset schizophrenia were randomly divided into aripiprazole group （n = 60） and risperidone group （n = 60） for eight therapeutic weeks. The positive and nega- tive syndrome scale （PANSS） was evaluated 8 weeks before and after therapy. The plasma PRL level was measured by using radioimmunoassay before and after 8-week therapy. The DRD3 Ser9Gly was genotyped using the polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP） method. Results There was no signifi- cant difference in the reduced rates of total scores of PANSS after 8 weeks between aripiprazole group and risperidone group （59.79±23.48 vs. 63.30 ±22.66, P 〉 0.05）. The plasma PRL level increased after 8-week risperidone therapy, while reduced after aripiprazole therapy [ （26.92±9.48） vs. （-25.25 ±8.07）, P 〈 0.05 ]. There was no signifi- cant association of the reduce rate of PANSS with different genotypes in either risperidone （RIS） or aripiprazole （ARI） group [ARI CC ＋ CT （57.83±19.94） vs. TT （56.84 ± 18.46）; RIS CC ＋ CT （53.94 v 21.08） vs. TT （60.38±19.37）, P 〉 0.05 ]. In contrast, there was an association of plasma PRL levels with the DRD3 Ser9Gly polymorphism in RIS group （CC ＋ CT [ （52.48 ± 27.01） vs. TT 36.07 ± 17.46, P 〈 0.01 ] but not in the ARI group [CC ＋ CT （-23.27 ±8.36]vs.TT （-26.05 ±8.11 ）, P 〉 0.05]. Conclusion Aripipazole is as effective as risperidone in the treatment of female patients with first-onset schizophrenia. Compared with aripipazole, risperidone tends to increase prolaciin levels, which might be influenced by the DRD3 polymorphism.