G蛋白β3亚单位基因多态性与奥氮平所致体重增加的相关性

摘要

目的：探讨G蛋白β3亚单位（G-proteinβ3 subunit，GNB3）基因C825T多态性与精神分裂症患者使用奥氮平治疗过程中体重增加的关系。方法对90例首次住院的精神分裂症患者予奥氮平治疗12周，监测治疗前后的体重、体重指数（body mass index，BMI）变化，并检测患者GNB3基因C825T多态性，分析基因多态性与体重变化的相关性。结果治疗后患者体重、BMI增加有统计学意义（均P<0.01）。TT基因型者治疗后的增重率（weight gain rate，WGR）及BMI增加较CC基因型者更明显（均P<0.01），携T等位基因（TT型+CT型）者治疗后的WGR及BMI增加较非携T等位基因（CC型）者更明显（均P<0.01）。治疗后WGR≥7%者GNB3基因C825T基因型分布（CC型15.69%，CT型54.90%，TT型29.41%）与WGR<7%者（CC型38.46%，CT型43.59%，TT型17.95%）差异有统计学意义（P<0.05），WGR≥7%者T等位基因频率（63.33%）高于WGR<7%者（39.74%）（P<0.05）。多因素线性回归显示TT基因型（以CC型为参照）影响奥氮平治疗后的体重变化（β=1.83，标准化β=0.29，P<0.01）。结论 GNB3基因C825T多态性与奥氮平所致的体重增加有关。%Objective To explore the relationship between G-protein β3 subunit (GNB3) gene C825T polymor⁃phism and the weight gain of schizophrenics treated with olanzapine. Methods Ninety schizophrenics of first time hospi⁃talization were collected and treated with olanzapine for 12 weeks. The changes of body weight and body mass index (BMI) were detected before and after 12-week olanzapine treatment. The GNB3 gene C825T polymorphism in patients was determined by polymerase chain reaction (PCR) and DNA sequencing technique. The correlation of GNB3 gene C825T polymorphism and change of clinical parameters was analyzed. Results Body weight and BMI in patients were all increased significantly after treatment (all P<0.01). Weight gain rate (WGR) and increase of BMI in the TT genotype group were higher than those in the CC genotype group (all P<0.01). WGR and increase of BMI in the T-allele carrier (TT and CT genotypes) were higher than those in the T-allele non-carrier (CC genotype) (all P<0.01). There was signifi⁃cant difference in distribution of genotypes between WGR ≥7% group (CC 15.69%, CT 54.90%, TT 29.41%) and WGR <7% group (CC 38.46%, CT 43.59%, TT 17.95%) (P<0.05). The frequency of T-allele in the WGR≥7% group (63.33%) was higher than that in the WGR<7%group (39.74%) (P<0.05). Multi-variable linear regression indicated that TT genotype (contrasted with CC genotype) was an influential factor for change of body weight after treatment with olan⁃zapine (β=1.83, standardized β=0.29, P<0.01). Conclusions The GNB3 gene C825T polymorphism is associated with olanzapine-induced weight gain.