抗精神病药物所致体重增加与5-羟色胺2C受体基因启动子区域多态性的关联

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

作者信息

Zhang Zhijun, Zhang Xiaobin, Yao Zhijian, Chen Jianfang, Sun Jing, Yao Hui, Hou Gang, Zhang Xinbao, Reynolds Gavin P

机构信息

Psychiatry Department and Clinical Science Center, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2002 Aug 25;82(16):1097-101.

PMID:12425817

Abstract

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 approximately 12 kg or -7.8% approximately 32%. The frequency of mutant hemizygote was 58% among the 58 male subjects; the frequency of mutant homozygote was 0%, and the frequency of mutant heterozygote 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 (chi(2) = 22.35, v1, P = 0.000 1; chi(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.

摘要

目的

确定5-羟色胺2C（5-HT2C）受体基因759C/T多态性是否影响精神分裂症患者抗精神病药物（APS）治疗后的体重增加。

方法

从117例符合CCMD-II-R标准诊断的汉族首发精神分裂症中国患者的外周血中提取DNA。采用PCR-RELP技术分析5-HTR2C受体基因759C/T半合子（男性）和基因型（女性）的频率。给予APS（氯丙嗪或利培酮）单药治疗10周。记录每位患者入院时及随后每周的体重，并计算体重指数（BMI）。分析半合子或基因型与BMI的相关性。

结果

治疗10周后，体重平均增加（3.2±3.5）kg，或为基线体重的（5.7±6.2）%，范围为-7 kg至12 kg或-7.8%至32%。58名男性受试者中突变半合子的频率为58%；59名女性受试者中突变纯合子的频率为0%，突变杂合子的频率为27.0%。体重增加>7%的情况在53%的野生型半合子男性和47%的野生型纯合子女性中出现；而在突变半合子男性中仅为18%，突变杂合子女性中为13%。体重增加>7%和体重<7%的患者中，759T半合子男性或杂合子女性的比例存在显著差异（χ²=22.35，v1，P = 0.0001；χ²=12.36，v1，P = 0.0001）。无突变等位基因的患者体重显著增加的可能性是有突变等位基因患者的五到六倍（OR = 5.11，6.68）。