黑素皮质素受体4基因rs489693位点多态性与慢性精神分裂症患者疗效、BMI及高血糖的关系

Association of MC4R(rs489693) polymorphism with clinical response, BMI and hyperglycemia of chronic schizophrenic patients

目的探讨黑素皮质素4受体(melanocortin four receptor, MC4R)rs489693多态性对奥氮平治疗后精神分裂症患者临床疗效、BMI、糖脂代谢的影响。方法选取135例慢性精神分裂症患者,根据DNA测序法检测MC4R基因489693位点的多态性分为AA组19例,AC组46例,CC组55例,于基线、治疗4、8、12周末对所有研究对象行PANSS量表测试,于治疗前和治疗12周末测定研究对象BMI、腰围及血糖、血脂水平,比较3组间各变量的差异。结果重复测量方差分析发现AA组、AC组、CC组的PANSS各项有时间主效应(P均<0.01);治疗12周末AA组净增体质量、净增BMI大于AC组(P=0.017,0.031)和CC组(P均<0.01);净增BMI百分比(%)、血糖(P=0.040)及糖化血红蛋白(P=0.026)AA组均大于CC组(P<0.01);研究治疗前后3组未见严重不良反应。结论 MC4R基因rs489693的AA基因型可能是奥氮平治疗慢性精神分裂症患者发生肥胖和高血糖的风险因素。

Objective To investigate the association of melanocortin four recepltor(MC4 R) rs489693 polymorphism on the clinical response, BMI, glucose and lipid metabolism of patients with chronic schizophrenia. Methods One hundred and thirty-five patients with chronic schizophrenia treated with oral olanzapine were enrolled in the study. According to the genotypes of MC4 R(rs489693) detected by DNA sequencing there were 19 patients with AA genotype, 46 patients with AC and 55 patients with CC. The Positive and Negative Syndrome Scale(PANSS scale) was assessed at baseline, after 4, 8 and 12 weeks of treatment;the BMI, waist, blood lipid, fasting blood glucose, glycosylated hemoglobin were measured at baseline and 12 weeks after treatment. The differences of items between the three groups before and after treatment were compared. Results ANOVA for repeated measurement revealed that the items of PANSS had a significant main effect of time in all three groups(all P<0.01). After 12 weeks of treatment, weight gain and absolute BMI increase of AA group were higher than that in AC group(P=0.017,0.031) and CC group(all P<0.01), and the AA group showed higher relative BMI gain(% of baseline) than the CC group(P<0.01). After 12 weeks of treatment, the values of the AA group in blood glucose(P=0.040) and glycosylated hemoglobin(P=0.026) were higher than those in the CC group. There was no severe adverse reactions in three groups. Conclusion The MC4 R rs489693 AA genotype may be a risk factor for olanzapine-related weight gain and hyperglycemia in patients with chronic schizophrenia.