瘦素基因启动子区-2548G／A功能多态性与抗精神病药源性肥胖的核心家系关联研究  

-2548G/A functional polymorphism in the promoter region of leptin gene and antipsychotic agent-induced weight gain in schizophrenic patients:a study of nuclear family-based association

作　　者：牟晓冬[1] 张志珺[1] 张向荣[2] 史家波[2] 孙静[2] 

机构地区：[1]东南大学附属中大医院神经科,南京210009 [2]南京医科大学附属脑科医院精神科,南京210029

出　　处：《中南大学学报（医学版）》2008年第4期316-320,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(30170344)~~

摘　　要：目的:探讨瘦素(leptin)基因启动子区-2548G/A功能多态性是否与首次抗精神病药物(antipsychotic agents,APS)治疗精神分裂症(schizophrenia,SCH)患者急性期体质量增加相关。方法:APS(利培酮或氯丙嗪)单药治疗10周,治疗前后测量体质量并计算体质量指数(body mass index,BMI)。采用PCR-RFLP技术分析84例首次治疗精神分裂症患者(包含完整核心家系70个)瘦素基因-2548 G/A基因型和等位基因分布频率,APS治疗所致体质量增加与瘦素-2548G/A多态性的关联分析及核心家系关联分析,采用传递不平衡检验(TDT)和数量性状传递不平衡检验(QTDT)。结果:治疗后患者体质量增加是基础体质量的(8.00±6.13)%。体质量增加≥7%和<7%患者组间瘦素基因-2548G/A多态性的等位基因在两组的分布差异有统计学意义(χ2=4.031,P=0.045)。核心家系分析采用TDT发现,在体质量增加≥7%组患者组存在传递不平衡,等位基因A更多的由杂合子父母传递给体质量增加≥7%的患者。结论:瘦素基因启动子区-2548G/A功能多态性与APS急性期治疗致精神分裂症患者体质量增加相关,-2548A等位基因可能是APS治疗所致肥胖的危险因素。Objective To investigate whether there is association between the -2548G/A functional polymorphism in the promoter region of leptin gene and we agents （ APS ） acute treatment in schizophrenic patients. Methods E t gain following antipsychotic t-four Chinese Han untreated schizophrenia patients in 70 nuclear families were recruited. The polymorphism of leptin gene was de- termined with PCR-RFLP technique. Body weight was measured in the patients on admission the and after 10 weeks treatment with risperidone or chlorpromazine. Results There was an average （ 8.00 ± 6. 13 ） % increases in baseline weight after the 10 week treatment. There were significant differences in the distribution of allele frequencies changed ≥ 7 % and 〈 7 % subgroups. （ χ^2 = 4.031, P = 0. 045 ） between the patients with weight Family-based association analysis further confirmed the above significant finding by transmission disequilibrium test but not by quantitative trait transmission disequi- librium test. Conclusion The finding confirms that the -2548G/A polymorphism in promoter region of leptin gene is associated with APS-induced weight gain.

关 键 词：瘦素 功能基因多态性 体质量增加 抗精神病药物 核心家系 

分 类 号：R749.3[医药卫生—神经病学与精神病学]