载脂蛋白E基因多态性与利培酮所致体质量降低的关联研究

Association analysis of apolipoprotein E polymorphisms and weight loss among schizophrenia patients with risperidone treatment

目的:探讨载脂蛋白E(apolipoprotein E,APOE)基因多态性与精神分裂症(schizophrenia,SZ)患者抗精神病药物治疗所致体质量变化的关联。方法:调查并随访1 516例首发SZ患者使用利培酮、阿立哌唑、喹硫平、氯氮平、奥氮平、奋乃静治疗2至7周后的体质量变化。使用TaqMan基因分型技术检测APOE基因多态性,应用Cox比例风险模型分析APOE基因变异与SZ患者药物治疗所致体质量变化之间的关系。结果:研究结果显示,在使用利培酮药物治疗患者中,rs7412位点相加模型增加体质量降低风险,HR(95%CI)为1.78(1.01-3.14),P=0.045。在使用利培酮药物治疗患者中,rs405509位点AC/CC基因型携带者相比AA基因携带者体质量降低的风险升高,HR(95%CI)为1.75(1.02-2.98),P=0.04。在除利培酮以外的其他药物治疗患者中,未发现rs769450,rs7412和rs405509不同基因型(相加模型、显性模型和隐性模型)与体质量增加、体质量降低的发生风险存在统计学关联,P值均>0.05。分层分析结果显示,在基线体质量正常组以及基线体质量超重或肥胖中,rs7412和rs405509不同基因型(相加模型、显性模型和隐性模型)与体质量降低的发生风险无异质性,P值均>0.05。结论:APOE基因rs7412和rs405509位点变异增加了SZ患者服用利培酮所致体质量降低的风险;临床应关注基线体质量正常患者APOE基因rs7412 C>T、rs405509A>C变异与利培酮所致体质量降低。

AIM:To explore the association between apolipoprotein E(APOE)gene polymorphisms and weight change in schizophrenia(SZ)patients induced by antipsychotic treatment.METHODS:1 516 first-episode SZ patients treated with risperidone,aripiprazole,quetiapine,clozapine,olanzapine and perphenazine for 2 to 7 weeks were followed up.TaqMan genotyping technique was used to detect APOE gene polymorphisms.Cox regression was used to analysis the association between APOE gene variation and risk of weight change induced by drug treatment in SZ patients.RESULTS:The results showed that rs7412 increased the risk of weight loss in patients treated with risperidone,HR(95%CI)was 1.78(1.01-3.14)with P=0.045.In patients treated with risperidone,the risk of weight loss was higher in carriers of AG/GG genotype of rs405509 than in carriers of AA genotype,HR(95%CI)was 1.75(1.02-2.98),P value was 0.04.In SZ patients treated with other antipsychotic drugs,the associations between rs769450,rs7412 and rs405509 genotypes(additive model,dominant model and recessive model)with weight change were not found.There was no statistical association;all the P values were more than 0.05.Stratified analysis showed that there was no heterogeneity between rs7412 and rs405509 genotypes(additive model,dominant model and recessive model)and the risk of weight loss in baseline normal weight group and baseline overweight or obesity group(P>0.05).CONCLUSION:rs7412 and rs405509 of APOE increase the risk of weight loss in SZ patients treated by risperidone.Clinician should pay more attention to association between APOE gene rs7412 C>T,rs405509 A>C variations and risperidone-induced weight loss in normal body weight patients.