Study On The Association Of Cytochrome P450 1A1 Gene With Endometriosis

Background Endometriosis is one of the most common benign gynecologic disorders. The pathogenesis is not completely understood. It is likely that endometriosis is a genetic disease which caused by an interaction between multiple gene loci and the environmental factors. Recent studies have shown that exposure to the dioxin is associated with an increased prevalence and severity of endometriosis. But the molecular mechanism of the connection between dioxin and endometriosis is not clear. Cytochrome P450 1A1(CYP1A1) gene, which is dioxin target gene, is expressed predominantly in extrahepatic human tissues, such as lung, placenta and uterus. The products of CYP1 Al gene which has been shown to be induced by dioxin in turn may activate chemically dioxin. In addition, The products of CYP1A1 gene can catalyze the metabolic transformation of estrogen. The CYP1 Al gene has been found to be polymorphic in human populations, and this determines interindividual variation of CYP1A1 enzyme activity. In recent years, with the further study on association of endometriosis with dioxin, it was attached more importance to the rble of CYP1A1 in pathogenesis of endometriosis. Nevertheless, the connection between CYP1 Al and endometriosis is not clear. Objective1. To investigate the expression of CYP1A1 messenger ribonucleic acid (mRNA) in endometriotic tissues and uterine endometrium from women with and without endometriosis throughout the menstrual cycle so as to determine whether C YP1A1 contribute to the pathogenesis of endometriosis.2. To investigate the gene polymorphisms of CYP1A1 in women with and without endometriosis and to assess the possible association between gene polymorphisms of CYP1 Al and the susceptibility to endometriosis. Methods and Results1. Thirty-five ectopic endometrium specimens (including 27 ovarianendometrioma and 8 uterosacral ligament nodule) and 28 eutopic endometrium specimens were biopsied from 30 patients with endometriosis (study group). Another 20 specimens of endometrium were biopsied from women without endometriosis (control group). Level of CYPlAl mRNA in the above endometriotic and eutopic endometrial tissues was determined by semi-quantitative reverse transcript-polymerase chain reaction (RT-PCR). The study demonstrated that there was no statistically significant difference in the levels of CYPlAl mRNA expression between the eutopic endometrium of woman with endometriosis(0.40 ?0.12) and endometrium of women without endometriosis (0.38+0.11), while the level of CYPlAl mRNA expression in ectopic endometrium(0.59 ?.15) was higher than those in eutopic endometrium of woman with endometriosis and endometrium of women without endometriosis (P < 0.05, respectively). Within the ectopic endometrium, the levels of CYPlAl mRNA expression at stage III/TV (According to the revised American Fertility Society classification) were higher than those at stages I/II (P<0.05). No significantly different expression of CYPlAl mRNA was found between secretive phase and proliferative phase, not only in ectopic endometrium and eutopic endometrium of study group but also in endometrium of control group.2. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and Allele-specific Polymerase chain reaction (AS-PCR) method were used to analyze the polymorphisms of CYPlAl gene in 76 patients with endometriosis (study group) and 80 women without endometriosis (control group). Two groups were chosen form Han women in Guangdong Province. The frequency of allele G on A4889G locus of CYPlAl gene showed a significant difference between the study cohort and the control group( x2=7.49, P<0.01), with an odds ratio (OR) of 1.96. Statistically significant difference in the frequencies of genotypes AA,AG and GG was observed between the two groups( x2=6.92, .P<0.05).Individuals with homozygotes for G allele had higher relative risk than those with homozygotes for A allele, with an OR of 3.44( x²=5.43, .P<0.05). The distribution of CYP1A1 gene Msp I genotyp...