中山地区难治性精神类疾病患者CYP2D6基因多态性及代谢表型的分布研究

Study on distribution of CYP2D6 gene polymorphism and metabolic phenotype in patients with refractory mental illness in Zhongshan area

目的探讨中山地区难治性精神类疾病患者CYP2D6基因多态性及代谢表型分布,并分析性别之间的差异。方法选取2018年1月至2020年4月在该院住院的难治性精神类疾病患者175例,根据《国际疾病分类》第10版疾病诊断标准将患者分为精神分裂症组(A组,106例)、心境障碍组(B组,38例)和其他精神疾病组(C组,31例)。采用Agena Bioscience Mass ARRAY DNA质谱基因分型方法,分析175例难治性精神类疾病患者的CYP2D6基因多态性(rs5030865、rs5030867、rs201377835、rs35742686、rs1080985、rs5030655、rs5030862、rs1135835、rs1081003、rs5030656、rs28371706、rs1065852、rs3892097、rs28371725、rs16947和rs1135840)及代谢表型(超快代谢型、广泛代谢型、中间代谢型和慢代谢型),比较3组CYP2D6基因型及表型分布频率和特征。结果所有检测对象中,CYP2D6基因16个位点中14个位点(rs16947、rs1080985、rs5030867、rs5030656、rs201377835、rs5030862、rs28371706、rs28371725、rs1065852、rs3892097、rs1135835、rs35742686、rs5030655和rs5030865)的基因频率的平衡检测差异均无统计学意义(P>0.05),具有区域群体代表性;而2个位点(rs1081003和rs1135840)基因频率的平衡检测差异有统计学意义(P<0.05)。CYP2D6基因16个位点中不同基因型在性别间及组间分布差异无统计学意义(P>0.05)。不同表型的组间分布差异有统计学意义(P<0.05),在性别间的分布差异无统计学意义(P>0.05)。结论该研究初步探讨了中山地区难治性精神类疾病患者CYP2D6基因多态性及代谢表型分布,有助于临床合理用药。

Objective To investigate the distribution of CYP2D6 gene polymorphism and metabolic phenotypes in the patients with refractory mental diseases in Zhongshan area,and to analyze their gender differences.Methods One hundred and seventy-five patients with refractory mental diseases admitted in this hospital from January 2018 to April 2020 were selected and divided into the schizophrenia group(group A,106 cases),mood disorder group(group B,38 cases)and other mental diseases group(group C,31 cases)according to the ICD-10 disease diagnosis criteria.The Agena Bioscience Mass ARRAY DNA mass spectrometry genetic typing method was used to analyze the CYP2D6 gene polymorphism(rs5030865,rs5030867,rs201377835,rs35742686,rs1080985,rs5030655,rs5030862,rs1135835,rs1081003,rs5030656,rs28371706,rs1065852,rs3892097,rs28371725,rs16947 and rs1135840)and metabolic phenotypes(ultra-fast metabolic type,extensive metabolic type,moderate metabolic type and poor metabolic type)in 175 patients with refractory mental diseases.The distribution frequency and characteristics of CYP2D6 genotype and phenotype were compared among the three groups.Results Among all the tested subjects,there was no statistically significant differences in the balance detection of gene frequency of 14 loci(rs16947,rs1080985,rs5030867,rs5030656,rs201377835,rs5030862,rs28371706,rs28371725,rs1065852,rs3892097,rs1135835,rs35742686,rs5030655 and rs5030865)among the 16 loci of CYP2D6 gene,which was representative of the local population;however,the difference in gene frequency balance detection between the two loci(rs1081003 and rs1135840)was statistically significant(P<0.05).There was no statistically significant difference in the distribution of different genotypes in 16 loci of CYP2D6 gene between genders and among the groups(P>0.05).There were significant differences in the distribution of different gene phenotypes among different groups(P<0.05).There was no significant difference in gene phenotype distribution among different genders(P>0.05).Conclusion The study has the preliminary investigation of CYP2D6 gene polymorphism and metabolic phenotype distribution in the patients with refractory mental diseases in Zhongshan area,which is helpful for clinical rational drug use.