中国健康人群与精神分裂症患者细胞色素P450 2C19/P450 2D6遗传多态性的比较

CYP2C19/CYP2D6 Genetic Polymorphisms in Chinese Healthy and Schizophrenia Populations

目的探讨中国健康人群与精神分裂症患者细胞色素P450 2C19(CYP2C19)/P450 2D6(CYP2D6)遗传多态性的相关性。方法应用PCR与DNA测序相结合的方法,对88名符合ICO-10诊断标准的精神分裂症患者和283名健康志愿者进行了CYP2C19基因多态性分析。同时用此方法对87名精神分裂症患者与93名健康志愿者进行了CYP2D6的基因多态性分析。根据CYP2C19*2(G681A)将精神分裂症患者和健康志愿者基因型分为3组(G/G,G/A,A/A);同样方法将CYP2C19*3(G636A)和CYP2D6(C100T)基因型各分为3组。结果在CYP2C19的检测中,健康志愿者中共检测到6个基因型,在精神分裂症患者中检测到7个基因型。2组间等位基因型差异没有统计学意义(CYP2C19*2χ2=4.954,P>0.05;CYP2C19*3χ2=2.334,P>0.05)。但发现精神分裂症患者突变型纯合子A/A的基因型频率明显高于健康志愿者。在CYP2D6(C100T)的基因型和等位基因型检测中,精神分裂症患者和健康志愿者组间的基因型和等位基因差异无统计学意义(χ2=0.202,P>0.05;χ2=0.066,P>0.05)。结论中国精神分裂症患者与健康人群在细胞色素氧化酶CYP2C19/CYP2D6遗传多态性上差异无统计学意义,CYP2C19*2的突变型纯合子可能是中国精神分裂症患者的一个易感因素。

Objective To investigate whether cytochrome P450 2C19 （CYP2C19） /P450 2D6 （CYP2D6） genetic polymorphisms were associated with schizophrenia in Chinese subjects. Methods 88 schizophrenics meeting criteria ICO-10 were enrolled in the study group and 283 healthy volunteers were involved in the control group. Polymerase chain reaction （PCR） and DNA sequencing were used to examine the CYP2C19（CYP2C19 ＊ 2/CYP2C19 ＊ 3 ）. Use the same methods to detect CYP2D6（C100T） genetic polymorphisms of 87 schizophrenics meeting criteria ICO-10 and 93 healthy volunteers. The patients and healthy volunteers were divided into three groups acceding to the CYP2C19 ＊ 2（G681A） genotypes（G/G, G/A, A/A）, the same as CYP2C19 ＊ 3 （G636A） and CYP2D6（C100T）. Results Six different allelic variants of CYP2C19 gene were observed in the control group and seven different allelic variants of CYP2C19 gene were detected in the schizophrenia group. There is no statistically significant difference in the allele frequencies of CYP2C19 ＊ 2 （X2 = 4.954, P 〉 0.05 ） and CYP2C19 ＊ 3 （X2 = 2. 334, P 〉 0.05 ） between schizophrenia and healthy volunteers. We found the frequency of the homozygote of CYP2C19 ＊ 2 in schizophrenia was conspicuously higher than that of healthy volunteers, There is no significant difference between two groups in CYP2D6（C100T） genotypes and alleles. Condusion Although there is no evidence to show the correlation between CYP2C19/CYP2D6（C100T） genetic polymorphisms and etiology of schizophrenia, the homozygote of CYP2C19 ＊ 2 is possible a genetic susceptibility factor in Chinese subjects with schizophrenia.