共济失调蛋白2结合蛋白1基因多态性与奥氮平所致体重增加的关联研究

Association of A2BP1 Gene Polymorphism with Olanzapine Induced Bodyweight Gain

目的：既往研究表明,共济失调蛋白2结合蛋白1（A2BP1）基因多态性可能与精神分裂症、孤独症及肥胖等复杂疾病关联,但目前尚无相关文献提示A2BP1基因多态性与抗精神病药所致体重增加的关联。本研究拟探讨A2BP1基因多态性与奥氮平治疗精神分裂症所致体重增加的关联。方法：本研究共入组350例精神分裂症患者,其中完成奥氮平（治疗剂量5~20 mg/d）治疗8周者为328例。采用阳性与阴性症状量表（PANSS）减分率评估药物疗效;分别于治疗前和治疗8周后测量并记录患者的清晨空腹体重并计算治疗前后体重增加率（%）。提取患者外周血DNA,采用DNA测序基因分析方法,在328例汉族精神分裂症患者中,检测A2BP1基因4个单核苷酸多态性（SNP）位点（rs8048076,rs1478697,rs10500331,rs4786847）的基因型,并采用数量性状位点分析方法（QTL）探索A2BP1基因多态性与奥氮平治疗所致体重增加率的关联。结果：A2BP1基因rs8048076（T=3.237;P=0.0012）及rs1478697（T=2.956;P=0.0032）位点与奥氮平治疗精神分裂症8周后所致体重增加率关联（P〈0.05）,经多重检验Bonferroni校正后仍有统计学意义;而rs10500331（T=-0.293;P=0.769）与rs4786847（T=0.666;P=0.505）在本样本中与奥氮平所致体重增加的关联无统计学意义（P〉0.05）。结论：本研究结果提示在中国汉族人群中,A2BP1基因多态性可能与奥氮平治疗精神分裂症患者所致体重增加副反应关联,如能进一步验证及机制探索,则有望在精神科个体化治疗方面对药物所致体重增加的预测与防治提供线索依据。

Objectives： Previous literatures indicated that A2BP1 might be one of the susceptibility genes of schizophrenia,autism,obesity and other complex diseases.However,up to now,there has not been any literatures reported the correlation between A2BP1 polymorphisms and bodyweight gain related to antipsychotic drugs treatment.Our objective was to explore the correlation between A2BP1 gene polymorphism and olanzapine induced weight gain.Methods： Three hundred and fifty patients with schizophrenia were enrolled in the present study.Among them,328 patients with schizophrenia were followed-up for 8-week therapy of olanzapine（5~20 mg/d）.The reduced scores of PANSS scale were used to assess the therapeutic effects of olanzapine.On the other hand,the bodyweight（kg） of 328 patients were measured before and after 8-week treatment of olanzapine.Four single nucleotide polymorphisms（SNPs： rs8048076,rs1478697,rs10500331,rs4786847） of the A2BP1 gene were genotyped using the direct DNA sequencing method.By using the QTL analysis,the association of A2BP1 polymorphisms with bodyweight gain induced by therapy of olanzapinewere explored.Results： We found significant association between rs8048076（T = 3.237;P = 0.0012）,rs1478697（T = 2.956;P = 0.0032） of A2BP1 and bodyweight gain change after 8-week olanzapine treatment（P0.05）.The two SNPs remained significant with bodyweight gain after the Bonferroni multiple correction.However,the association of the other 2 SNPs were not significant with bodyweight gain induced by olanzapine therapy,rs10500331（T =-0.293;P = 0.769）,rs4786847（T = 0.666;P = 0.505）,respectively.Conclusion： A2BP1 gene polymorphism was associated with olanzapine induced weight gain in Chinese Han population.Moreover,A2BP1 might be a susceptible locus to explore the mechanism of body weight gain induced by antipsychotics induced and also might be helpful for the individual therapy of psychiatric treatment.