中国汉族健康人群多巴胺D1受体-48A/G基因多态性与精神分裂症的相关性

Association between dopamine D1 receptor-48A/G gene polymorphism and schizophrenia in healthy Chinese Han population

目的:探讨中国汉族健康人群多巴胺D1受体-48A/G基因多态性与高加索、德国及日本健康人群和精神分裂症患者的差异。方法:收集2004-03/07在武汉大学人民医院精神卫生中心和武汉市第二精神病医院住院治疗的精神分裂症患者117例(精神分裂症组)及同期体检的中国健康汉族人188例(对照组),均来自湖北省,无血缘关系。分析-48A/G基因型在不同种族间(中国汉族与高加索、德国及日本人群)、精神分裂症患者和正常人群、不同家族史精神分裂症患者和正常人群的分布差异,采用聚合酶链反应-限制性片段长度多态性法。结果:有117例精神分裂症患者和188例正常人的样本纳入结果分析。①不同种族间多巴胺D1受体-48A/G基因型分布的比较:中国汉族健康人群-48A/G等位基因的分布高于高加索和德国人群,低于日本人群(χ2=65.728,18.281,9.929;P均<0.01);在基因型的分布上,与日本人群差异也存在显著性(χ2=8.191,P<0.01)。②精神分裂症组和对照组多巴胺D1受体-48A/G基因多态性分布的比较:两组基因型分布及等位基因均差异无显著性(χ2=1.179,0.072,P均>0.05)。③不同家族史精神分裂症组和对照组多巴胺D1受体-48A/G基因多态性分布的比较:有精神分裂症家族史患者AA基因型频率高于对照组(91.7%和71.3%,χ2=6.621,P<0.01),A等位基因频率明显高于对照组(69/72和320/376,χ2=6.081,P<0.05)。结论:中国汉族健康人群与文献报道的高加索、德国及日本人群多巴胺D1受体-48A/G等位基因分布存在显著性差异,在基因型的分布上,与日本人群也存在显著性差异;精神分裂症患者和正常人群的基因型频率和等位基因频率的分布相似;有精神分裂症家族史患者AA基因型频率及A等位基因频率明显高于正常人群,提示中国汉族人群中多巴胺D1受体-48A/G基因多态性可能与精神分裂症发病有关,A等位基因可能是精神分裂症发病的风险因子之一。

AIM： To investigate the difference of dopamine D1 receptor -48A/G gene polymorphism between a healthy Chinese Han population and the Caucasian, German and Japanese healthy populations and schizophrenic patients. METHODS： Between March and July 2004, 117 schizophrenic inpatients （schizophrenia group） in the Mental Health Center, Renmin Hospital of Wuhan University and Wuhan Second Psychiatric Hospital and 188 Chinese Han healthy physical examinees （control） participated in the study, all were from Hubei province and had no blood relationship. The differences of the distribution of -48A/G genotype were analyzed between different races （Chinese Han population and Caucasian, German and Japanese）, between schizophrenic patients and healthy population, also between schizophrenic patients with different family history and healthy population with the method of polymerase chain reaction-restriction fragment length polymorphism. RESULTS： All the 117 schizophrenic patients and 118 healthy people were involved in the analysis of results. ①Comparison of the distribution of dopamine D1 receptor -48A/G genotype between different races： The distribution of -48A/G allele in healthy Chinese Han population was higher than those in Caucasian and German populations, but lower than that in Japanese population （X^2=65.728, 18.281, 9.929; P 〈 0.01）, there was also significant difference in the distribution of genotype between healthy Chinese Han population and Japanese population （X^2=8.191, P 〈 0.01）. ②Comparison of the distribution of dopamine D1 receptor -48A/G gene polymorphism between the schizophrenia group and control group： There were insignificant differences in the distributions of genotype and allele between the two groups （X^2=1.179, 0.072, P 〉 0.05）. ③Comparison of the distribution of dopamine D1 receptor -48A/G gene polymorphism between the schizophrenic patients with different family history and control group： The AA genotypic frequency of the patients with schizophrenic history was higher than that in the control group （91.7%, 71.3%, ,X^2=6.621, P 〈 0.01）, and the frequency of A allele was obviously higher than that in the control group （69/72, 320/376, X^2=6.081, P 〈 0.05）. CONCLUSION： Healthy Chinese Han population have significantly different distribution of dopamine D1 receptor -48A/G allele from those in Caucasian, German and Japanese populations as reported, also have significant different genotypic distribution from that in Japanese population. The distributions of genotypic frequency and allele frequency are similar between schizophrenic patients and normal population. The AA genotypic frequency and the frequency of A allele are obviously higher in the patients with schizophrenic family history than in normal population, it is indicated that the dopamine D1 receptor -48A/G gene polymorphism in Chinese Han population may be associated with the attack of schizophrenia, and A allele may be one of the risk factors for the attack of schizophrenia.