代谢酶基因多态性对孕期妇女尿中1-羟基芘水平的影响

Influence of Metabolic Enzymes Genetic Polymorphisms on Urinary 1-hydroxypyrene Concentrations in Pregnant Women

目的探讨代谢酶基因多态性对孕期妇女尿1-羟基芘(1-OHPy)水平的影响。方法于2006年10月—2008年1月,在太原市两所二级甲等综合性医院中随机调查符合条件的孕期妇女347名,进行流行病学调查和生物样品的收集。采用高效液相色谱法测定尿样中1-羟基芘水平,应用多重PCR和限制性内切酶PCR(RFLP-PCR)技术分析四种代谢酶基因多态性(GSTM1,GSTT1,GSTP1,CYP1A1MspⅠ)。结果校正年龄、教育水平等因素后,携带CYP1A1纯合突变基因型的孕期妇女其尿样1-OHPy水平(1.6530μmol/molCr)明显高于野生型(1.1624μmol/molCr),差异有统计学意义(P=0.047);携带GSTP1纯合突变基因型的孕期妇女尿样1-OHPy水平(1.1721μmol/molCr)明显高于野生型(0.8679μmol/molCr),差异有统计学意义(P=0.009);多基因模型中,CYP1A1和GSTP1对孕期妇女尿样1-OHPy浓度具有修饰作用(P=0.046,P=0.029),多基因模型的决定系数为0.262;基因-基因交互作用分析显示对尿中1-OHPy浓度有修饰作用的多态位点主要有CYP1A1和GSTM1。结论代谢酶基因多态性在PAHs体内代谢中具有修饰作用,CYP1A1、GSTP1基因多态性对于孕期妇女体内芘代谢中可能起着重要作用,CYP1A1与GSTM1对芘的代谢具有交互作用。

Objective To analyze the effects of the GSTM1 ,GSTF1 ,GSTP1 and CYP1A1 genotypes on urinary 1-hydroxypyrene in the pregnant women. Methods During the period of October 2006 to January 2008,347 pregnant women living in Taiyuan were randomly selected to join the project. The urine samples were collected before giving birth and the maternal blood was collected within one day postpartum. High-performance liquid chromatography （HPLC） with subsequent fluorescence detection was used to determine the urine 1-hydroxypyrene levels. Genomic DNA was extracted from lymphocytes by standard techniques. The genotyping of CYP1A1 MspI, GSTM1, GSTrl and GSTP1 was performed in duplicate, using techniques based on PCR or PCRRFLP. Results After controlling for several factors, 1-OHPy level was significantly higher in the urine of mothers with CYP1A1 homozygous at CC （1.653 0 umol/mol Cr） than that （1.162 4 umol/mol Cr） in wild genotype （P=0.047）. And the mothers with homozygous GG at GSTP1 had a significantly higher level of 1-OHPy （1.172 1 umol/mol Cr） compared with the wild genotype group （0.867 9 umol/mol Cr, P=0.009）; CYP1A 1 and GSTP1 could modify the 1-OHPy concentration in the multi-gene model. R2=0.262; Urinary 1-OHPy concentration could be influenced by CYP1A 1 and GSTP1 polymorphisms in the analysis of two way gene-gene interaction. Conclusion Genetic polymorphisms may play an important role in modulating the PAHs -metabolizing. CYP1A land GSTP1 genotypes are associated with urine 1-OHPy concentration and there are interactive effects between CYP1A1 and GSTM1 genotype on the 1-OHPy levels.