细胞色素P450酶1A2、2D6与多巴胺D2受体基因多态性对奥氮平治疗精神分裂症PANSS减分率的影响

目的 研究细胞色素P450酶(cytochromeSP450, CYP)1A2、2D6以及多巴胺D2(dopamine receptorSD2, DRD2)受体的基因多态性对奥氮平治疗精神分裂症阳性和阴性症状量表(positive and negative syndrome scale, PANSS)减分率的影响及其程度。方法 入组只用奥氮平治疗的精神分裂症住院患者178例,评定治疗前以及治疗4周后的PANSS量表得分,计算减分率。同时,收集血液,测定CYP1A2*1F、CYP2D6*10、DRD2 -141C Ins/Del、DRD2 -241 A>G、DRD2 Taq1A位点的基因多态性。通过方差分析,比较各基因型PANSS减分率的差异；通过多元线性回归分析,得出减分率的回归方程,并计算决定系数。结果 PANSS减分率在CYP1A2*1F(CC：65.68±11.22,CA：55.59±15.40,AA：43.75±15.20)、CYP2D6*10(CC：44.36±16.67,CT：51.78±17.81,TT：56.14±17.13)、DRD2 -141C Ins/Del(Ins/Ins：55.11±17.39,Ins/Del：39.16±14.28)和DRD2 -241 A>G(AA：45.47±17.52,GA：61.82±10.55,GG：75.43±17.71)不同基因型之间均有统计学显著差异(均P<0.01),而DRD2 Taq1A位点的基因型间PANSS减分率差异无统计学意义(P>0.05)。 PANSS减分率＝58.041-10.703╳CYP1A2*1F+4.272╳CYP2D6*10-11.921╳DRD2 -141C Ins/Del +13.443╳DRD2 -241 A>G(决定系数R_²＝0.517,P<0.05)。结论 CYP1A2*1F、CYP2D6*10、DRD2-141 C Ins/Del、DRD2-241A>G位点基因多态性影响奥氮平治疗精神分裂症疗效,但只解释了减分率的51.7%,有待纳入更多的影响因素进行分析。

Influence of Genetic Polymorphisms of Cytochrome P450 1A2, 2D6 and Dopamine Receptor D2 on the Reduction Rate of PANSS Score of Olanzapine Treatment for Schizophrenia

OBJECTIVE To explore the influence of genetic polymorphisms of cytochrome P450(CYP) 1A2, 2D6 and dopamine receptor D2(DRD2) on the reduction rate of positive and negative syndrome scale(PANSS) score of olanzapine treatment for schizophrenia. METHODS One hundred seventy eight cases of schizophrenia inpatients treated with olanzapine were recruited. PANSS were evaluated at baseline and 4 weeks after olanzapine treatment. The PANSS total score reduction rates were calculated. Meanwhile, their blood was collected for genetic polymorphism detections of CYP1A2*1F, CYP2D6*10, DRD2-141C Ins/Del, DRD2-241 A>G and DRD2 Taq1A. The difference of PANSS score reduction rates among genotypes in each gene were compared by analysis of variance, and its regression equation was obtained by multivariate linear regression analysis. RESULTS The PANSS reduction rates among genotypes in CYP1A2*1F(CC:65.68±11.22, CA:55.59±15.40, AA:43.75±15.20), CYP2D6*10(CC:44.36±16.67; CT:51.78±17.81; TT:56.14±17.13), DRD2-141C Ins/Del(Ins/Ins:55.11±17.39, Ins/Del:39.16±14.28) and DRD2-241 A>G (AA:45.47±17.52; GA:61.82±10.55; GG:75.43±17.71) were obviously different(all P<0.01). However, the reduction rates in DRD2 Taq1A genotypes did not show a significant change(P>0.05). PANSS reduction rate=58.041-10.703×CYP1A2*1F+4.272×CYP2D6*10-11.921×DRD2-141C Ins/Del+13.443×DRD2-241A>G(R²=0.517, P<0.05). CONCLUSION Genetic polymorphisms of CYP1A2*1F, CYP2D6*10, DRD2-141 C Ins/Del, and DRD2-241A>G can influence efficacy of olanzapine treatment for schizophrenia patients, but they only accounted for 51.7% of the reduction. More influencing factors are needed to be included for analysis.