Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain

作者：Mueller D J; Zai C C; Sicard M; Remington E; Souza R P; Tiwari A K; Hwang R; Likhodi O; Shaikh S; Freeman N; Arenovich T; Heinz A; Meltzer H Y; Lieberman J A; Kennedy J L

来源：The Pharmacogenomics Journal, 2012, 12(2): 156-164.

DOI：10.1038/tpj.2010.65

• antipsychotic-induced weight gain
• schizophrenia
• pharmacogenetics
• dopamine receptor genes
• polymorphisms
• haplotypes

Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with most antipsychotics. We have conducted the first in-depth examination of dopamine receptor genes in antipsychotic-induced weight gain. A total of 206 patients (139 of European descent and 56 African Americans) who underwent treatment for chronic schizophrenia or schizoaffective disorder were evaluated after on average over 6 weeks of treatment. Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1-DRD5) were analyzed. In the total sample, we found a nominally significant association between the DRD2 rs1079598 marker and weight change using a cutoff of 7% gain (P = 0.03). When stratifying the sample according to ethnicity and antipsychotics with highest risk for weight gain, we found significant associations in three DRD2 SNPs: rs6277 (C957T), rs1079598 and rs1800497 (TaqIA). The other genes were primarily negative. We provide evidence that dopamine receptor DRD2 gene variants might be associated with antipsychotic-induced weight gain in chronic schizophrenia patients. The Pharmacogenomics Journal (2012) 12, 156-164; doi:10.1038/tpj.2010.65; published online 17 August 2010

• 出版日期2012-4