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Science China Life Sciences

, Volume 62, Issue 4, pp 535–543 | Cite as

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

  • 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 LiEmail author
  • Chinese Antipsychotics Pharmacogenomics Consortium
Research Paper
  • 10 Downloads

Abstract

Antipsychotic-induced metabolic disturbance (AIMD) is a common adverse effect of antipsychotics with genetics partly underpinning variation in susceptibility among schizophrenia patients. Melanocortin4 receptor (MC4R) 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 MC4R 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-naïve/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-naïve 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.

Keywords

MC4R antipsychotics metabolic disturbance 

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Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China Key Project (91332205, 81130024, 81630030 to T.L.), 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.), National Natural Science Foundation of China (8157051859 to W.D. et al.), Sichuan Science & Technology Department (2015JY0173 to Q.W.), and 1.3.5 Project for disciplines of excellence, West China Hospital of Sichuan University (ZY2016103, ZY2016203 to T.L.). This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yamin Zhang
    • 1
    • 2
  • Hongyan Ren
    • 1
    • 2
  • Qiang Wang
    • 1
    • 2
  • Wei Deng
    • 1
    • 2
  • Weihua Yue
    • 3
    • 4
  • Hao Yan
    • 3
    • 4
  • Liwen Tan
    • 5
  • Qi Chen
    • 6
  • Guigang Yang
    • 7
  • Tianlan Lu
    • 3
    • 4
  • Lifang Wang
    • 3
    • 4
  • Fuquan Zhang
    • 8
  • Jianli Yang
    • 9
    • 10
  • Keqing Li
    • 11
  • Luxian Lv
    • 12
  • Qingrong Tan
    • 13
  • Hongyan Zhang
    • 3
    • 4
  • Xin Ma
    • 6
  • Fude Yang
    • 7
  • Lingjiang Li
    • 5
  • Chuanyue Wang
    • 6
  • Dai Zhang
    • 3
    • 4
  • Liansheng Zhao
    • 1
    • 2
  • Huiyao Wang
    • 1
    • 2
  • Xiaojing Li
    • 1
    • 2
  • Wanjun Guo
    • 1
    • 2
  • Xun Hu
    • 14
  • Yang Tian
    • 1
    • 2
  • Xiaohong Ma
    • 1
    • 2
  • Tao Li
    • 1
    • 2
    Email author
  • Chinese Antipsychotics Pharmacogenomics Consortium
  1. 1.Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of BiotherapyWest China Hospital of Sichuan UniversityChengduChina
  2. 2.West China Brain Research CenterWest China Hospital of Sichuan UniversityChengduChina
  3. 3.Peking University Sixth Hospital (Institute of Mental Health)BeijingChina
  4. 4.National Clinical Research Center for Mental Disorders & Key Laboratory of Mental HealthMinistry of Health (Peking University)BeijingChina
  5. 5.Second Xiangya HospitalCentral South UniversityChangshaChina
  6. 6.Beijing Anding Hospital, Beijing Institute for Brain DisordersCapital Medical UniversityBeijingChina
  7. 7.Beijing HuiLongGuan HospitalBeijingChina
  8. 8.Wuxi Mental Health CenterNanjing Medical UniversityWuxiChina
  9. 9.Institute of Mental HealthTianjin Anding HospitalTianjinChina
  10. 10.Tianjin Medical University General Hospital, Tianjin Medical UniversityTianjinChina
  11. 11.Hebei Mental Health CenterBaodingChina
  12. 12.Second Affiliated Hospital of Xinxiang Medical UniversityXinxiangChina
  13. 13.Department of Psychiatry, Xijing HospitalFourth Military Medical UniversityXi’anChina
  14. 14.Huaxi BiobankWest China Hospital of Sichuan UniversityChengduChina

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