Testing the role of genetic variation of the MC4R gene in Chinese population in antipsychotic-induced metabolic disturbance  

作　　者：Yamin Zhang Hongyan Ren Qiang Wang Wei Deng Weihua Yue Hao Yan Liwen Tan Qi Chen Guigang Yang Tianlan Lu Lifang Wang Fuquan Zhang Jianli Yang Keqing Li Luxian Lv Qingrong Tan Hongyan Zhang Xin Ma Fude Yang Lingjiang Li Chuanyue Wang Dai Zhang Liansheng Zhao Huiyao Wang Xiaojing Li Wanjun Guo Xun Hu Yang Tian Xiaohong Ma Tao Li Chinese Antipsychotics Pharmacogenomics Consortium 

机构地区：[1]Mental Health Center and Psychiatric Laboratory,the State Key Laboratory of Biotherapy,West China Hospital of Sichuan University,Chengdu 610041,China [10]Tianjin Medical University General Hospital,Tianjin Medical University,Tianjin 300070,China [11]Hebei Mental Health Center,Baoding 71000,China [12]Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002,China [13]Department of Psychiatry,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China [14]Huaxi Biobank,West China Hospital of Sichuan University,Chengdu 610041,China [2]West China Brain Research Center,West China Hospital of Sichuan University,Chengdu 610041,China [3]Peking University Sixth Hospital(Institute of Mental Health),Beijing 100191,China [4]National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health,Ministry of Health(Peking University),Beijing 100191,China [5]5Second Xiangya Hospital,Central South University,Changsha 410011,China [6]Beijing Andi ng Hospital,Beijing Institute for Brain Disorders,Capital Medical University,Beijing 100088,China [7]Beijing HuiLongGuan Hospital,Beijing 100096,China [8]Wuxi Mental Health Center,Nanjing Medical University,Wuxi 214151,China [9]Institute of Mental Health,Tianjin Anding Hospital,Tianjin 300070,China [15]不详

出　　处：《Science China(Life Sciences)》2019年第4期535-543,共9页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China Key Project(91332205,81130024,81630030to T.L.);National Natural Science Foundation of China(8157051859 to W.D.et al.);National Key Technology R&D Program of the Ministry of Science and Technology of China(2016YFC0904300 to T.L.);National Natural Science Foundation of China/Research Grants Council of Hong Kong Joint Research Scheme(8141101084 to T.L.);Sichuan Science&Technology Department(2015JY0173 to Q.W.);1.3.5 Project for disciplines of excellence,West China Hospital of Sichuan University(ZY2016103,ZY2016203 to T.L.)

摘　　要：Antipsychotic-induced metabolic disturbance(AIMD) is a common adverse effect of antipsychotics with genetics partly underpinning variation in susceptibility among schizophrenia patients. Melanocortin4 receptor(MC4 R) gene, one of the candidate genes for AIMD, has been under-studied in the Chinese patients. We conducted a pharmacogenetic study in a large cohort of Chinese patients with schizophrenia. In this study, we investigated the genetic variation of MC4 R in Chinese population by genotyping two SNPs(rs489693 and rs17782313) in 1,991 Chinese patients and examined association of these variants with the metabolic effects that were often observed to be related to AIMD. Metabolic measures, including body mass index(BMI), waist circumference(WC), glucose, triglyceride, high-density lipoprotein(HDL), and low-density lipoprotein(LDL) levels were assessed at baseline and after 6-week antipsychotic treatment. We found that interaction of SNP×medication status(drug-na?ve/medicated) was significantly associated with BMI, WC, and HDL change %, respectively. Both SNPs were significantly associated with baseline BMI and WC in the medicated group. Moderate association of rs489693 with WC, Triglyceride, and HDL change % were observed in the whole sample. In the drug-na?ve group, we found recessive effects of rs489693 on BMI gain more than 7%, WC and Triglyceride change %, with AA incurring more metabolic adverse effects. In conclusion, the association between rs489693 and the metabolic measures is ubiquitous but moderate. Rs17782313 is less involved in AIMD. Two SNPs confer risk of AIMD to patients treated with different antipsychotics in a similar way.Antipsychotic-induced metabolic disturbance(AIMD) is a common adverse effect of antipsychotics with genetics partly underpinning variation in susceptibility among schizophrenia patients. Melanocortin4 receptor(MC4 R) gene, one of the candidate genes for AIMD, has been under-studied in the Chinese patients. We conducted a pharmacogenetic study in a large cohort of Chinese patients with schizophrenia. In this study, we investigated the genetic variation of MC4 R in Chinese population by genotyping two SNPs(rs489693 and rs17782313) in 1,991 Chinese patients and examined association of these variants with the metabolic effects that were often observed to be related to AIMD. Metabolic measures, including body mass index(BMI), waist circumference(WC), glucose, triglyceride, high-density lipoprotein(HDL), and low-density lipoprotein(LDL) levels were assessed at baseline and after 6-week antipsychotic treatment. We found that interaction of SNP×medication status(drug-na?ve/medicated) was significantly associated with BMI, WC, and HDL change %, respectively. Both SNPs were significantly associated with baseline BMI and WC in the medicated group. Moderate association of rs489693 with WC, Triglyceride, and HDL change % were observed in the whole sample. In the drug-na?ve group, we found recessive effects of rs489693 on BMI gain more than 7%, WC and Triglyceride change %, with AA incurring more metabolic adverse effects. In conclusion, the association between rs489693 and the metabolic measures is ubiquitous but moderate. Rs17782313 is less involved in AIMD. Two SNPs confer risk of AIMD to patients treated with different antipsychotics in a similar way.

关 键 词：MC4R ANTIPSYCHOTICS METABOLIC DISTURBANCE 

分 类 号：Q[生物学]