5-HTR2C基因多态性对奥氮平治疗精神分裂症患者糖脂代谢的影响

Effects of 5-HTR2C Gene Polymorphisms on Glucolipid Metabolism in Schizophrenia Patients Treated with Olanzapine

关键词:  精神分裂症  奥氮平  5-HTR2C  基因多态性  糖脂代谢

Key words:  schizophrenia  olanzapine  5-HTR2C  gene polymorphism  glycolipid metabolism

摘要:

目的 探讨5-羟色胺2C受体(5-hydroxytryptamine 2C receptor,5-HTR2C)基因-759C/T和-697G/C位点多态性对奥氮平治疗精神分裂症患者糖脂代谢的影响。方法 纳入184例接受奥氮平单一治疗的精神分裂症住院患者为研究对象,于基线及治疗第6周末测定患者空腹血糖(fastingbloodglucose,FBG)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)及高密度脂蛋白(high density lipoprotein,HDL)水平,运用多重高温连接酶检测反应技术检测5-HTR2C基因-759C/T和–697G/C基因多态性,采用协方差分析比较不同基因型治疗前后糖脂水平的变化。结果 5-HTR2C基因–759C/T和–697G/C位点各基因型基线糖脂代谢指标差异无统计学意义;治疗6周后,–759C/T位点基因型间FBG和TG净增差异有统计学意义(F=4.862,P=0.009;F=3.397,P=0.036),其中FBG净增野生CC型患者高于CT或TT型患者(P=0.038,P=0.010),TG净增野生CC型患者高于TT型患者(P=0.010);–697G/C位点基因型间FBG净增差异有统计学差异(F=4.385,P=0.014),其中野生GG型患者高于CC型患者(P=0.006);两位点联合分析也发现,野生CC/GG基因型患者FBG净增高于CT+TT/GC+CC基因型患者(P=0.021)。结论 5-HTR2C基因–759C/T和–697G/C位点多态性与奥氮平治疗精神分裂症患者引起糖脂代谢异常具有一定相关性。

Abstract:

OBJECTIVE To investigate the effects of -759 C/T and -697 G/C polymorphisms of 5-hydroxytryptamine 2 C receptor gene(5-HTR2 C) on glucolipid metabolism in schizophrenia patients treated with olanzapine.METHODS A total of 184 schizophrenia patients who treated with olanzapine alone were recruited. Fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TC), low density lipoprotein(LDL) and high density lipoprotein(HDL) were measured at baseline and the end of 6 th week of treatment. The -759 C/T and -697 G/C polymorphisms of 5-HTR2 C gene were detected by improved multiple ligase detection reaction(iMLDR), and then the changes in glycolipid levels before and after treatment for each genotype were compared by covariance analysis.RESULTS There was no significant difference in baseline glucolipid levels between -759 C/T and -697 G/C genotypes of 5-HTR2 C gene. There were significant differences in net increase of FBG and TG between -759 C/T genotypes after 6 weeks of treatment(F=4.862, P=0.009; F=3.397, P=0.036). The net increase of FBG in patients with wild CC genotype was higher than that in patients with CT or TT genotypes(P=0.038, P=0.010), and the net increase of TG in patients with wild CC genotype was higher than that with TT genotype(P=0.010). There was significant difference in the net increase of FBG between -697 G/C genotypes(F=4.385, P=0.014), and patients with wild GG genotype was higher than that with CC genotype(P=0.006). The combined analysis of the two loci also found that the net increase of FBG in patients with wild CC/GG genotype was higher than that in patients with CT+TT/GC+CC genotype(P=0.021).CONCLUSION The -759 C/T and -697 G/C polymorphisms of 5-HTR2 C gene are associated with abnormal glucolipid metabolism in schizophrenia treated with olanzapine.