CYP1B1基因多态性与妊娠期肝内胆汁淤积症易感性的关系

目的研究CYP1B1基因外显子2密码子119(G-T)和外显子3密码子432(C-G)多态性与妊娠期肝内胆汁淤积症(ICP)发病的关系。方法分别应用等位基因特异性PCR(AS-PCR)技术和人工修饰双等位基因特异性引物扩增(diASA-AMP)法,对100例ICP患者和100例正常对照孕妇CYP1B1基因外显子2密码子119(G-T)和外显子3密码子432(C-G)多态性进行分析。结果1CYP1B1基因密码子119多态分析表明ICP组T等位基因频率高于对照组(P<0.05),ICP组基因型GG、GT、TT频率与对照组相比差异有统计学意义(P<0.05)。与野生型(GG)相比,ICP组GT基因型和TT基因型增加ICP的发病风险(OR值分别为2.435和3.600);2CYP1B1基因密码子432多态分析表明两组均未检测到GG突变型,基因型CC、CG频率和等位基因C、G频率的比较差异均无统计学意义(P>0.05)。结论CYP1B1基因外显子2密码子119多态性可能与成都地区ICP易感性有关。

Association of Gene Polymorphisms of CYP1B1 with Intrahepatic Cholestasis of Pregnancy

OBJECTIVE: To study the role of gene polymorphisms of cytochrome P4501B1 (CYP1B1) in exon 2 codon 119(G-T) and exon 3 codon 432(C-G) in intrahepatic cholestasis of pregnancy (ICP). METHODS: Gene polymorphisms of CYP1B1 in exon 2 codon 119 and exon 3 codon 432 were detected with Allele-specific polymerase chain reaction (ASA-PCR) and di-allele-specific-amplification with artificially modified primer (diASA-AMP) techniques in a case-control study, which included 100 ICP patients and 100 healthy pregnant women as controls. RESULTS: (1) The ICP patients had higher frequency of allele T on codon 119 of CYP1B1 gene than the controls (P < 0.05). Significant differences of frequencies were found in genotype GG, GT and TT between the ICP patients and the controls (P > 0.05). Compared to the wide-type GG, the ICP risks of the women with genotype TT homozygous and GT heterozygous increased by 3.6 and 2.435 times, respectively. (2) No genotype GG was found in this study. There were no significant differences between the ICP patients and the controls in the genotype distributions (CC and CG) and allele frequencies (C and G) of CYP1B1 polymorphism in exon 3 codon 432 (P > 0.05). CONCLUSION: Gene polymorphism of CYP1B1 in exon 2 codon 119 may be associated with the risk of ICP. The mutation of CYP1B1 gene increases the risk of ICP. The gene polymorphism of CYP1B1 in exon 3 codon 432 is not associated with the risk of ICP.