title: A2BP1 gene polymorphisms association with olanzapine-induced weight gain.
abstract: The ataxin-2 binding protein 1 (A2BP1) gene is reported to be one of the susceptibility genes in schizophrenia, autism, and obesity. The aim of this study was to explore the association of A2BP1 gene polymorphisms with antipsychotic induced weight gain (AIWG) in Chinese Han population. Three hundred and twenty-eight patients with schizophrenia were followed-up for an 8-week period of treatment with olanzapine. The fasting weights of 328 patients were measured before and after the 8-week course of treatment. Four single nucleotide polymorphisms (SNPs: rs8048076, rs1478697, rs10500331, and rs4786847) of the A2BP1 gene were genotyped by polymerase chain reaction (PCR). We analyzed putative association of A2BP1 polymorphisms with AIWG of olanzapine using linear regression analysis and found that SNP rs1478697 was significantly associated with AIWG caused by olanzapine (p=0.0012; Bonferroni corrected p=0.0048). The association was replicated in another independent sample including 208 first-episode and drug-naïve patients presenting with schizophrenia after a 4-week treatment with olanzapine (p=0.0092; Bonferroni corrected p=0.0368; meta p=5.33×10(-5)). To explore the biological plausibility of A2BP1 in the pathogenesis of AIWG, we made expression analyses and eQTL analyses; these analyses showed that A2BP1 was highly expressed in whole brain tissues using the HBT database, and that rs1478697 has an expression quantitative trait locus effect in human cerebellar cortex tissues using the BRAINEAC database (p=2.50E-04). In conclusion, the rs1478697 in A2BP1 may be associated with AIWG induced by 8-week treatment with olanzapine.
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Licai
authors.initials: L
authors.lastname: Dong
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, 453002, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaoning, 121013, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Ma
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei, 071000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Du
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaoning, 121013, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jin
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, 453002, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, 453002, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Mi
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaoning, 121013, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei, 071000, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, 453002, China.
authors.forename: Luxian
authors.initials: L
authors.lastname: Lv
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China; Peking-Tsinghua Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, Sixth Hospital, Peking University, Beijing, 100191, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Centerfor Mental Disorders (Peking University), Beijing, 100191, China. Electronic address: dryue@bjmu.edu.cn.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D001569:Benzodiazepines / Q000009:adverse effects*; D001921:Brain / Q000378:metabolism; D002681:China; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Antipsychotic induced weight gain; Ataxin-2 binding protein 1; Olanzapine; Schizophrenia