腺苷酸环化酶基因多态性与双相躁狂患者急性期药物治疗临床应答差异研究

Study on Difference in Clinical Responses between Gene Polymorphism of Adenylate Cyclase and Drug Therapy for Patients with Bipolar Mania at Acute Stage

目的:探讨腺苷酸环化酶基因多态性是否与双相躁狂患者急性期药物治疗临床应答有关。方法:选取2016年5月至2019年1月在徐州市东方人民医院诊断为双相躁狂急性期的患者103例及同期健康志愿者60例。患者入组前采用急性期倍克-拉范森狂躁量表(Bech-Rafaelsen mania rating scale,BRMS)和双相障碍临床疗效总评量表-严重程度分量表(CGI-BP-S)进行访谈,并检测两组患者ADCY2基因rs2230739位点的等位基因。入组后采用碳酸锂和喹硫平联合治疗,于治疗前后观察患者的BRMS、副反应量表(treatment emergent symptom scale,TESS)评分。根据不同基因型,分析患者治疗后BRMS评分情况。结果:ADCY2基因rs2230739位点共检出G、A两种等位基因,包括GG、GA和AA三种基因型。双相躁狂组患者与健康志愿者基因型的差异无统计学意义(χ^2=3.949,P=0.139)。治疗2、4及8周结束时,患者BRMS评分较治疗前明显降低,差异均有统计学意义(t=36.483,P=0.000;t=45.772,P=0.000;t=11.005,P=0.000)。经过8周治疗,患者的总有效率为93.2%(96/103)。治疗2周后,三种基因型患者BRMS评分的差异有统计学意义(F=4.410,P=0.015),其中GG型与GA型患者BRMS评分的差异有统计学意义(P=0.004)。治疗4周后,三种基因型患者BRMS评分的差异有统计学意义(F=4.819,P=0.010),其中GG型与GA型(P=0.004)、GG型与AA型(P=0.047)患者BRMS评分的差异有统计学意义。治疗8周后,三种基因型患者BRMS评分的差异有统计学意义(F=5.289,P=0.007),其中GG型与GA型(P=0.002)、GG型与AA型(P=0.047)患者BRMS评分的差异有统计学意义。结论:碳酸锂联合喹硫平治疗双相躁狂急性期的疗效显著,ADCY2基因rs2230739位点多态性与患者的疗效有关联,且三种基因型对碳酸锂和喹硫平易感性顺序为GG型>GA型>AA型。

OBJECTIVE:To probe into whether the gene polymorphism of adenylate cyclase is associated with the clinical response of drug therapy for patients with bipolar mania at acute stage.METHODS:Totally 103 patients diagnosed with bipolar mania at acute stage admitted into Xuzhou Dongfang People's Hospital and 60 healthy volunteers from May 2016 to Jan.2019 were selected.The patients were interviewed with Bech-Rafaelsen mania rating scale(BRMS)and CGI-BP-S before enrolled,the alleles of rs2230739 locus in ADCY2 gene of the two groups were detected.The patients were given lithium carbonate combined with quetiapine for treatment,the BRMS and treatment emergent symptom scale(TESS)scores of patients were observed before and after treatment.According to different genotypes,the BRMS scores of patients after treatment were analyzed.RESULTS:Two types of alleles(G and A)were detected at the rs2230739 locus in ADCY2 gene,including three genotypes(GG,GA and AA).There was no statistical significance in difference in genotypes between bipolar mania group and healthy volunteer group(χ^2=3.949,P=0.139).At 2,4 and 8 weeks after treatment,the BRMS score of patients were significantly lower than that of before treatment,with statistically significant differences(t=36.483,P=0.000;t=45.772,P=0.000;t=11.005,P=0.000).After 8-week treatment,the total effective was 93.2%(96/103).After 2-week treatment,the differences in BRMS scores among three genotypes were statistically significant(F=4.410,P=0.015),of which the difference in BRMS scores between GG type and GA type was statistically significant(P=0.004).After 4-week treatment,the differences in BRMS scores among three genotypes were statistically significant(F=4.819,P=0.010),of which the differences in BRMS scores between GG type and GA type(P=0.004),GG type and AA type(P=0.047)were statistically significant.After 8-week treatment,the differences in BRMS scores among three genotypes were statistically significant(F=5.289,P=0.007),of which the differences in BRMS scores between GG type and GA type(P=0.002),GG type and AA type(P=0.047)were statistically significant.CONCLUSIONS:The efficacy of lithium carbonate combined with quetiapine in treatment of bipolar mania at acute stag is remarkable,which is associated with the polymorphism of rs2230739 locus in ADCY2 gene,and the susceptibility of the three genotypes to lithium carbonate and quetiapine is GG type>GA type>AA type.