广东省中山地区汉族精神类疾病患者药物基因型及代谢表型分布研究

Research on Characteristics of Drug Genotypes and Metabolic Phenotypes in Chinese Han Patients with Severe Mental Illness in Zhongshan Area of Guangdong Province

目的探讨中山地区汉族重性精神类疾病患者药物基因型及代谢基因表型特征,为重性精神疾病临床个体化选药提供代谢基因型临床参考。方法随机选取2018年1月~2019年2月在中山市第三人民医院住院的患者155例,根据ICD-10疾病诊断标准将患者分为:精神分裂症组(A组,n=95)、心境障碍组(B组,n=30)和其他精神疾病组(C组,n=30)。采用飞行时间质谱检测技术,分析纳入患者的药物基因型和代谢表型,比较各基因型表型分布频率和特征。结果 155例样本中CYP2D6,CYP2C19和NAT2基因中间代谢型频率最多,分别为50.9%,52.9%和48.4%;CYP3A4基因全部为广泛代谢型(100%);CYP1A2基因发现两个表型,即超快代谢型(50.3%)和广泛代谢型(49.7%);CYP3A5,UGT2B15,UGT2B7和FKBP5基因型中突变纯合型频率最多,分别为51.6%,45.8%,53.6%和54.9%;而MC4R和DRD2基因型中野生纯合型频率最高,分别为61.9%和51.0%。HTR2A和HTR2C基因型在所测样本中突变杂合型频率最多,分别为47.1%和99.4%。三组间基因代谢表型比较发现CYP2C19慢代谢型和NAT2基因慢代谢型差异有统计学意义(χ^2=6.452~12.054,均P<0.05);三组间基因型比较发现CYP3A5基因野生纯合型、UGT2B15基因突变杂合型、MC4R基因突变杂合型和野生纯合型差异均有统计学意义(χ^2=5.907~12.40,均P<0.05)。结论中间代谢型和突变纯合型分别是中山市重性精神疾病患者药物基因代谢表型及基因型的主要特征。

Objective To map the characteristics of drug genotypes and metabolic phenotypes in Chinese Han patients with severe mental illness in Zhongshan city.Methods 155 patients with severe mental illnesses were randomly involved and phenotypic analysis for drug genotypes and metabolic phenotypes based on exfoliated cells from patients’ cheek were determined by time-of-flight mass spectrometry.The frequencies of individual genotype were calculated and the genetic characteristics were compared in the diagnosis-specific groups,including schizophrenia group(A),mood disorder group(B) and other mental illnesses group(C).Results The frequencies of intermediate homozygous in CYP2D6,CYP2C19 and NAT2,were mostly found in 50.9%,52.9% and 48.4% respectively.Frequency of widely metabolic phenotype were found at CYP3A4 genes predominately(100%).There were two phenotypes in CYP1A2,namely,ultrafast metabolic type(50.3%) and extensive metabolic type(49.7%).Most of homozygousgenotypes were identified in CYP3A5,UGT2B15,UGT2B7 and FKBP5 with frequencies of 51.6%,45.8%,53.6% and 54.9% respectively.The frequencies of wild homozygotes in MC4R and DRD2 genotypes were 61.9% and 51.0% respectively.There were the most mutation heterozygosity frequencies in HTR2A and HTR2C genotypes,which were 47.1% and 99.4% respectively.Metabolic phenotype comparison among the three groups showed significant differences in CYP2C19 slow metabolic type,NAT2 slow metabolic type(χ^2=6.452~12.054,all P<0.05).Genotype comparison among the three groups showed significant differences in CYP3A5 wild homozygous type,UGT2B15 mutation heterozygous type,MC4R mutation heterozygous type and wild homozygous type(χ^2=5.907~12.40,all P<0.05).Conclusion The intermediate homozygous and homozygous genotype are main characteristics for either drug genotypes or metabolic phenotypes for Chinese Han patients with severe mental illnesses at Zhongshan city.