抗精神病药物致体重增加与5羟色胺2C受体基因启动子区多态性的关系

Association of antipsychotic agent-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene

目的 探讨首发精神分裂症患者抗精神病药物 (APS)治疗过程中的体重增加与 5羟色胺 2C受体 (HTR2C)基因启动区 - 759C/T单核酸置换多态性有无相关。方法 采用PCR RFLP技术分析 1 1 7例首发精神分裂症患者 (男 58例 ,女 59例 )HTR2C基因 - 759C/T半合子 (男性 )或基因型 (女性 )分布频率 ,APS(利培酮或氯丙嗪 )单药治疗 1 0周 ,测定患者治疗前后的体重和体重指数 (BMI) ,并分析半合子或基因型与BMI变化值的相关性。结果 治疗后患者平均体重增加 (3 2± 3 5)kg或基础体重的 (5 7± 6 2 ) % ,体重变化范围为 - 7kg～ 1 2kg或 - 7 8%～ 32 %。 58例男性患者突变型半合子频率为 1 9% ,59例女性患者突变型纯合子频率为 0 % ,杂合子频率为 2 7 0 %。 - 759T半合子 (男性 )或杂合子 (女性 )在体重增加 >7%和体重增加 <7%的患者组分布差异有非常显著意义 (χ2 =2 2 35 ,P=0 0 0 0 1 ;χ2 =1 2 36 ,P =0 0 0 0 1 ) ;与携带 - 759T半合子或杂合子患者组相比 ,不携带者体重增加的危险度高 5～ 6倍 (OR =5 1 1 ,6 68)。结论 HTR2C基因启动区 - 759C/T单核酸置换多态性与APS治疗导致汉族精神分裂症患者体重增加相关联 ,而 - 759C→T单核酸置换是防止和限制体重增加的基因保护因素。

Objective To determine whether 5 hydroxytryptamine 2C (5 HT2C) receptor gene 759C/T polymorphism influences the weight gain following antipsychotic agents (APS) treatment in patient with schizophrenia. Methods DNA was extracted from the peripheral blood of 117 Chinese first episode patients of Han nationality with schizophrenia diagnosed according to CCMD II R criteria. PCR RELP technique was used to analyse the frequencies of 5 HTR2C receptor gene 759C/T hemizygote (male) and genotype (female). Monotherapy with APS (chlorpromazine or rispperidone) was given for 10 weeks. The body weight was taken and body mass index (BMI) was calculated on admission and every week subsequently for each patient. The correlation of hemizygote or genotype and the BMI was analyzed. Results Ten weeks after treatment, there was an average increase in body weight of (3 2 ± 3 5) kg or (5 7±6 2)% of the baseline weight with a range of -7 kg～12 kg or -7 8%～32% The frequency of mutant hemizygote was 58% among the 58 male subjects; the frequency of mutant homozygote was 0%, and the frquency of mutant heterpzygote was 27 0% among the 59 female subjects The body weight gain >7% occurred in 53% of wild type hemizygote males and 47% of wild type homozygote females; and only 18% of mutant hemizygote males and 13% of mutant heterozygote females. The proportions of 759T hemizygote males or heterozygote females in those with body weight gain >7% and those with body weight <7% were significantly different (χ 2=22 35,v1, P = 0 000 1; χ 2=12 36,v1, P = 0 000 1). Patients without mutant allele were five to six times more likely to develop substantial weight gain ( OR =5 11,6 68). Conclusion The 5 HT2C receptor gene -759C/T polymorphism is associated with APS induced weight gain. 759C→T may be a protective factor for the development of weight gain in Chinese schizophrenic patients of Han nationality.