Analysis of genetic variations in the dopamine D1 receptor (DRD1) gene and antipsychotics-induced tardive dyskinesia in schizophrenia

作者：Lai I Ching; Mo Geng Han; Chen Mao Liang; Wang Ying Chieh; Chen Jen Yeu; Liao Ding Lieh; Bai Ya Mei; Lin Chao Cheng; Chen Tzu Ting; Liou Ying Jay^*

来源：European Journal of Clinical Pharmacology, 2011, 67(4): 383-388.

DOI：10.1007/s00228-010-0967-2

• Dopamine receptor
• DRD1
• Schizophrenia
• Tardive dyskinesia
• Haplotype
• Genotype

Dyskinesia is a kind of abnormal involuntary movement disorder that increases with age. The pathogenesis of dyskinesia may result from divergent changes in dopamine D1 receptors (DRD1) and dopamine D2 receptors (DRD2) in the brain while aging. Tardive dyskinesia (TD), a kind of dyskinesia, may develop after long-term antipsychotic treatment. Because the prevalence of TD also steadily increased with age, TD has been suggested to be the consequence of an imbalance between DRD1 and DRD2. We supposed that patients who develop TD may have genetic variants of DRD1 that cause the excitatory effects of DRD1 overwhelming the attenuated inhibitory effects of DRD2 after antipsychotic treatment.
In the present study, schizophrenic inpatients receiving long-term antipsychotic treatment were first assessed using the Abnormal Involuntary Movement Scale (AIMS), and only patients who were either free of any abnormal involuntary movements (non-TD group, AIMS = 0) or who showed persistent TD (TD group) were enrolled. Finally, 382 patients were recruited (TD = 220, non-TD = 162) and three single nucleus polymorphisms (SNPs; rs5326, rs4532 and rs265975) of DRD1 were genotyped for each subject.
Genotype frequency (%; AA/AG/GG) of rs4532 (TD: non-TD) was 61.4/35.8/2.8: 74.2/24.5/1.3. After genetic analyses, genotype GG showed significant association with TD (if OR = 2.0, power (%) = 98.5; if OR = 1.5, power (%) = 63.7; P = 0.033). Haplotype frequency (%) CGC of rs5326-rs4532-rs265975 (TD: non-TD) was 19.0:13.7; and after haplotype-based analyses, haplotype CGC also showed significant association with TD (OR = 1.4, permutation P = 0.027).
Our results indicate that the genotypic variants of DRD1 might play a role in the susceptibility of TD. Further replication in other countries or other populations is highly expected.

• 出版日期2011-4
• 单位河北医科大学