An association study between dopamine D1 receptor gene polymorphisms and the risk of schizophrenia.

Abstract

Deficits in dopamine transmission at D1 receptors in the PFC are implicated in schizophrenia. Genetic polymorphisms in functional regions of DRD1 have a plausible role in modulating the risk of schizophrenia. In order to evaluate the role of DRD1 polymorphisms as a risk factor for schizophrenia, we performed a detailed analysis of possible functional single nucleotide polymorphisms (SNPs) in regulatory and coding regions of DRD1. Nine SNPs were identified by DNA sequencing in 20 patients with schizophrenia. Then 385 cases and 350 healthy control subjects were genotyped using the nine SNPs (rs4867798, rs686, rs1799914, rs4532 rs5326, rs265981, rs10078714, rs10063995, rs10078866). Statistically significant differences were observed in the allelic or genotypic frequencies of the rs686 and rs10063995 polymorphism in the DRD1 gene. A significantly lower risk of schizophrenia was associated with the G allele and AG+GG genotype of rs686 (OR (G allele)=0.632, 95%CI (G allele): 0.470-0.849; OR (AG+GG genotype)=0.578, 95%CI (AG+GG genotype): 0.416-0.803) compared with the A allele and AA genotype, respectively. And a significantly increased risk of schizophrenia was associated with the T allele of rs10063995 (OR=1.446, 95%CI: 1.125-1.859) compared with the G allele. The haplotype analysis indicated the G-T variant containing the T allele of rs10063995 is a risk for schizophrenia (P=0.005, OR=1.467, 95%CI: 1.123-1.917). These data suggest that DRD1 gene polymorphisms confer susceptibility to schizophrenia, and also support the notion that dysfunction of DRD1 is involved in the pathophysiological process of schizophrenia.

• Authors: Feng Zhu, Chun-xia Yan, Qian Wang, Yong-sheng Zhu, Yan Zhao, Jiong Huang, Hong-bo Zhang, Cheng-ge Gao, Sheng-bin Li
• Journal: Brain research (Brain Res) Vol. 1420 Pg. 106-13 (Oct 28 2011) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 21955727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Receptors, Dopamine D1

Topics

• Adult
• Alleles
• Confidence Intervals
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Odds Ratio
• Polymorphism, Single Nucleotide
• Receptors, Dopamine D1 (genetics)
• Schizophrenia (genetics)
• Young Adult