UGT和FMOs基因多态性对奥氮平临床疗效的关联分析  

Association analysis of UGT and FMOs gene polymorphisms on clinical efficacy of olanzapine

作　　者：刘克锋[1] 杜书章[1] 杨勇杰 乔高星 康建[1] 张晓坚[1] 赵杰[1] LIU Ke-feng;DU Shu-zhang;YANG Yong-jie;QIAO Gao-xing;KANG Jian;ZHANG Xiao-jian;ZHAO Jie(Department of Pharmacy,The First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052,Henan Province,China)

机构地区：[1]郑州大学第一附属医院药学部,河南郑州450052

出　　处：《中国临床药理学杂志》2023年第20期3000-3004,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划精准医学研究重点专项基金资助项目(2017YFC090990)。

摘　　要：目的 探讨尿苷二磷酸葡糖醛酸基转移酶1A4(UGT1A4)、尿苷二磷酸葡糖醛酸基转移酶2B10(UGT2B10)、黄素单氧化酶1(FMO1)、黄素单氧化酶3(FMO3)基因多态性与奥氮平临床疗效之间的关系。方法 104例精神分裂症患者均给予奥氮平5~20 mg·d^(-1)治疗6周。通过阳性和阴性症状量表(PANSS)来评估奥氮平治疗精神分裂症的疗效,按照PANSS减分率≥50%和<50%分为有效组和无效组。用Sequenom MassArray系统基因分型方法对患者检测UGT1A4(rs2011425)、UGT2B10(rs61750900)、FMO1(rs12720462)、FMO1(rs7877)、FMO3(rs2266780)基因多态性,用秩和检验分析基因多态性与临床疗效的关系;比较治疗前后患者体质量、尿素(Urea)、尿酸(UA)、谷丙转氨酶(GPT)、谷草转氨酶(GOT)、三酰甘油(TG)、血糖(GLU)、泌乳素(PRL)的变化。结果 治疗后,有效组81例,无效组23例。治疗前和治疗后第6周PANSS总分分别为80.25±7.01、42.18±2.92,差异有统计学意义(P<0.05)。治疗前、后患者体质量分别为(62.62±12.88)和(65.86±12.89)kg, GOT分别为(23.06±18.95)和(31.48±30.01)U·L^(-1),GPT分别为(24.61±26.11)和(46.12±67.34)U·L^(-1),TG分别为(1.01±0.53)和(1.28±0.62)mmol·L^(-1),PRL分别为(31.75±26.78)和(57.63±58.31)ng·mL^(-1),差异均有统计学意义(均P<0.05)。其中UGT1A4(rs2011425)基因有效组TT型占70.88%,TG型占29.12%,无效组TT型占69.57%,TG型占30.43%;FMO1(rs12720462)基因有效组CC型占52.78%,CA型占33.33%,无效组CC型占28.57%,CA型占61.90%;FMO1(rs7877)基因有效组CC型占58.44%,CT型占36.36%,无效组CC型占36.36%,CT型占59.09%;FMO3(rs2266780)基因有效组GA型占40.51%,AA型占58.23%,无效组GA型占30.43%,AA型占69.57%。FMO1(rs12720462)基因CC型与CA型比较,差异有统计学意义(P<0.05),UGT2B10(rs61750900)基因型均为GG型。结论 奥氮平会导致患者体质量增加,GPT、GOT、TG、PRL水平升高,奥氮平疗效与UGT1A4(rs2011425)、FMO1(rs7877)、FMO3(rs2266780)、UGT2B10(rs61750900)的基因多ObjectiveTo investigate the relationship between the polymorphisms of uridine diphosphate glucuronosyltransferase 1A4(UGT1A4),uridine diphosphate glucuronosyltransferase 2B10(UGT2B10),flavin-containing monooxygenase 1 (FMO1),flavincontaining monooxygenase 3 (FMO3) genes and the clinical efficacy of olanzapine.Methods 104 patients with schizophrenia were treated with olanzapine 5-20 mg·d^(-1)for 6 weeks.The efficacy of olanzapine in the treatment of schizophrenia was assessed by the positive and negative symptom scales (PANSS),which were divided into effective and ineffective groups according to PANSS reduction rates≥50%and50%.With Sequenom.The MassArray system genotyping method was used to detect the polymorphisms of UGT1A4 (rs2011425),UGT2B10 (rs61750900),FMO1 (rs12720462),FMO1 (rs7877) and FMO3 (rs2266780).The relationship between gene polymorphism and clinical efficacy was analyzed by rank sum test.The changes of body weight,Urea,uric acid (UA),glutamicpyruvic transaminase (GPT),alanine oxalacetic transaminase (GOT),triglyceride (TG),blood glucose (GLU) and prolactin (PRL) were compared before and after treatment.Results After treatment,81 cases were effective group and 23 cases were invalid group.Before treatment and sixth week after treatment,the total score of PANSS was80.25±7.01 and 42.18±2.92,and the difference was statistically significant (P0.05).The body weight before and after treatment were (62.62±12.88) and (65.86±12.89) kg,GOT were (23.06±18.95) and (31.48±30.01)U·L^(-1),GPT were (24.61±26.11) and (46.12±67.34) U·L^(-1),TG were (1.01±0.53) and (1.28±0.62)mmol·L^(-1),PRL were (31.75±26.78) and (57.63±58.31) ng·m L^(-1),respectively (all P0.05).Among them,TT genotype accounted for 70.88%and TG genotype accounted for 29.12%in the effective group of UGT1A4(rs2011425) gene,TT genotype accounted for 69.57%and TG genotype accounted for 30.43%in the ineffective group.FMO1 (rs12720462) CC genotype accounted for 52.78%and CA genotype accounted for 33.33%in the effective group,CC genotype a

关 键 词：奥氮平 尿苷二磷酸葡糖醛酸基转移酶1A4 尿苷二磷酸葡糖醛酸基转移酶2B10 黄素单氧化酶1 黄素单氧化酶3 基因多态性 精神分裂症 

分 类 号：R97[医药卫生—药品]