CYP 1B1基因A119S多态性与妊娠期肝内胆汁淤积症风险关系的研究

Study on the relationship between gene polymorphism of CYP1B1 A119S and risk of intrahepatic cholestasis of pregnancy

目的:探讨CYP1B1基因A119S多态性与妊娠期肝内胆汁淤积症(ICP)发生危险性的关系。方法:用等位基因特异性PCR(AS-PCR)法,对73例妊娠期肝内胆汁淤积症患者和90例正常女性的CYP1B1 A119S多态位点进行检测分析,确定出多态性的3种基因型,即野生型G/G、杂合型G/T、突变型T/T。结果:CYP1B1基因A119S多态性G/G、G/T、T/T 3种基因型分布频率,ICP组分别为3.8%、39.7%和16.5%,对照组分别为64.4%、26.7%和8.9%;ICP组G、T等位基因频率为63.7%,36.3%,对照组为77.8%,22.2%。CYP1B1 A119S多态性基因型及等位基因型在两组间分布频率的差别有统计学意义(P<0.05)。基因型T/T与G/G比较、G/T与G/G比较,OR值分别为2.719(1.007～7.341)倍和2.190(1.096～4.375)倍;等位基因T使ICP危险性增加了1.995(1.226～3.246)倍。结论:CYP1B1 A119S多态位点3种基因型的分布与ICP发病风险有一定关联,突变基因型增加了ICP的发病风险。

Objective： To explore the relationship between gene polymorphism of CYP1 B1 A119S and the occurrence of intrahepat- ie cholestasis of pregnancy （ICP） . Methods： Allele -specific polymerase chain reaction method （AS -PCR） was used to analyze gene polymorphism locus in exon 2 eodon 119 （G- T） of CYP1B1 in 73 cases with endometrial cancer and 90 normal women. Three genotypes were defined, including homozygous wild type （G/G） , heterozygous variant （G/T） , and homozygous variant （T/T） . Results： The preva- lence rates of CYP1B1 AllgS genotypes C/G, G/T, and T/T were 3.8%, 39. 7%, and 16. 5% in ICP group, 64. 4%, 26. 7%, and 8.9% in control group. The frequencies of CYP1B1 G and T alleles were 63.7% and 36. 3% in ICP group, 77.8% and 22. 2% in eontrol group, respectively. There were statistically significant differences in distribution frequencies of polymorphism genotypes and alleles of CYP1 B1 A119S between the two groups （ P 〈 0. 05 ） . Compared with G/C,, the OR value of T/T was 2. 719 （ 1. 007 - 7. 341 ）, the OR val- ue of GT was 2. 190 （ 1. 096 - 4. 375 ） , respectively. The risk of ICP in patients with T allele increased by 1. 995 times （ 1. 226 - 3.246） . Conclusion： The distributions of three gene polymorphism locus of CYP1 B1 have a eertain correlation with risk of ICP, mutant genotypes in- crease the risk of ICP.