Güzey Cüneyt, Lopez-Rodriguez Rosario, Myhre Ronny, Spigset Olav
Division of Psychiatry, Department of Research and Development, St. Olav University Hospital, Trondheim, Norway.
Genet Test Mol Biomarkers. 2011 Jul-Aug;15(7-8):557-63. doi: 10.1089/gtmb.2010.0210. Epub 2011 Mar 31.
Polymorphisms in genes coding for dopaminergic and serotonergic receptors and transporters have been associated with the clinical effects and adverse drug reactions of antipsychotic and antidepressant drugs. The objective of this study was to investigate the frequency and combinations of common polymorphisms in the dopamine transporter (DAT1), dopamine D(2) receptor (DRD2), dopamine D(3) receptor (DRD3), serotonin transporter (5HTT), and serotonin 2A receptor (5HTR2A) genes in a Norwegian population. To determine the background frequency in the population, 250 blood samples were consecutively collected from healthy Norwegian blood donors (125 men and 125 women; mean age: 48±11 years). Samples were tested for DAT1 VNTR, DRD2 Taq1A, DRD3 Ser9Gly, 5HTTLPR, and four polymorphisms (102 T>C, His452Tyr, 516 C>T, and Thr25Asn) in the 5HTR2A, using polymerase chain reaction and real-time polymerase chain reaction. We observed the frequency of the nine-repeat allele of DAT1 VNTR polymorphism as 20% (95% confidence interval [CI]: 0.18-0.23), the A1 allele of DRD2 Taq1A polymorphism as 21% (95% CI: 0.19-0.23), the A1 allele of DRD3 Ser9Gly polymorphism as 68% (95% CI: 0.66-0.70), the short allele of 5HTTLPR as 38% (95% CI: 0.36-0.40), and the T allele of 5HTR2A 102 T>C polymorphism as 41% (95% CI: 0.39-0.41), and the frequencies of 5HTR2A His452Tyr and 5HTR2A Thr25Asn were 93% and 95%, respectively. The tested polymorphisms showed differences compared with other European populations. Further studies are necessary to better understand the effect of these alleles and their combinations on personality, mental disorders, drug response, and adverse reactions of psychotropic drugs.
编码多巴胺能和5-羟色胺能受体及转运体的基因多态性与抗精神病药物和抗抑郁药物的临床疗效及药物不良反应相关。本研究的目的是调查挪威人群中多巴胺转运体（DAT1）、多巴胺D2受体（DRD2）、多巴胺D3受体（DRD3）、5-羟色胺转运体（5HTT）和5-羟色胺2A受体（5HTR2A）基因常见多态性的频率及组合情况。为确定该人群的背景频率，从健康的挪威献血者中连续采集了250份血样（125名男性和125名女性；平均年龄：48±11岁）。采用聚合酶链反应和实时聚合酶链反应对血样进行DAT1可变数目串联重复序列（VNTR）、DRD2 Taq1A、DRD3 Ser9Gly、5HTTLPR以及5HTR2A基因的4种多态性（102 T>C、His452Tyr、516 C>T和Thr25Asn）检测。我们观察到DAT1 VNTR多态性的九重复等位基因频率为２０％（95％置信区间[CI]：0.18 - 0.23），DRD2 Taq1A多态性的A1等位基因频率为21％（95％CI：0.19 - 0.23），DRD3 Ser9Gly多态性的A1等位基因频率为68％（95％CI：0.66 - 0.70），5HTTLPR的短等位基因频率为38％（95％CI：0.36 - 0.40），5HTR2A 102 T>C多态性的T等位基因频率为41％（95％CI：0.39 - 0.41），5HTR2A His452Tyr和5HTR2A Thr25Asn的频率分别为93％和95％。与其他欧洲人群相比，所检测的多态性存在差异。有必要开展进一步研究，以更好地了解这些等位基因及其组合对人格、精神障碍、药物反应和精神药物不良反应的影响。
