Testing the role of genetic variation of the MC4R gene in Chinese population in antipsychotic-induced metabolic disturbance
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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.
KeywordsMC4R antipsychotics metabolic disturbance
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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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