Study On The Association Between Estrogen Receptor Gene And Estrogen -metabolizing Genes Polymorphisms And Intrahepatic Cholestasis Of Pregnancy

[Objective] To investigate whether polymorphisms in estrogen receptor alpha (ER α) and estrogen-metabolizing genes (CYP17, CYP1A2, CYP3A4 and COMT) are associated with intrahepatic cholestasis of pregnancy (ICP) in Chengdu.[Methods] The Xba I and Pvu II polymorphism in intron 1 of ERα gene, the T 1931 C polymorphism in the 5' untranslated region of the CYP17 gene, a point mutation from G to A at position -2964 in the 5'-flanking region of CYP1A2 gene, the A-290 G polymorphism in the 5'-regulatory region of CYP3A4 gene and Val 158 Met polymorphism of COMT caused by the missense mutation of G 158 A in exon 4 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 pregnant women with ICP (ICP group) and 100 normal pregnant women(contral group) in Chengdu.[Results] (1) The genotype distributions and allele frequencies of ERα -Xba I and ER α -Pvu II polymorphisms were not significant different between ICP group and control group (P>0.05). There was also no significant difference in the frequency of Xba I and Pvu II haplotype between the two groups(P>0.05). (2) The genotype distributions and allele frequencies of CYP17 polymorphism were not significant different between ICP group and control group (P>0.05). (3) We didn't find any A(-290)G mutation of CYP3A4 among the 200 individuals studied. (4) The GA genotype of CYP1A2 significantly elevated risk of ICP (P=0.029, OR=1.896), so did the VV+VM genotypes of COMT (P=0.027, OR=3.996). Women with allele G of CYP1A2 and allele V of COMT simultaneously also had an significantly increased risk of ICP (P=0.011, OR=2.852).[Conclusion] The single nucleotide polymorphisms (SNPs) in estrogen-metabolizing genes CYP1A2 and COMT are associated with the susceptibility of ICP in Chengdu; But the SNPs of ER α , CYP17 and CYP3A4 genes are not related to the risk of ICP in Chengdu.