子宫内膜异位症患者AHSG基因突变及芳香酶P450表达的相关性研究

Association of the AHSG polymorphism with genetic susceptibility to stage Ⅳ endoametriosis and expression of aromatase P450 in eutopic and ectopic endometrium

目的：探讨子宫内膜异位症患者α2-Hs-糖蛋白（AHSG）基因突变及芳香酶P450在子宫内膜异位症患者内膜的表达。方法：以50例Ⅳ期子宫内膜异位症患者（评分〉40）及62例非子宫内膜异位症对照者的外周血白细胞为样本，利用聚合酶链反应（polymerase chain reaction，PER）技术分析了α2-Hs-糖蛋白（AHSG）基因突变。取对照组在位子宫内膜及Ⅳ期子宫内膜异位症患者在位及异位子宫内膜为标本，采用免疫组织化学方法测定各组内膜组织腺细胞中芳香酶P450的表达，根据阳性率和表达强度进行量化评分（组织化学评分）。结果：Ⅳ期子宫内膜异位症组中AHSG基因的三种基因型野生型（wide—type，W）、杂合型（wide—mutation，WM）、突变型（mutate—type，M）各占44％；46％、10％，而对照组则分别为71％、25．8％、3．2％。将突变型与杂合型合并与野生型比较，两组间差异有显著性（Χ^2=8．317，P=0．004），其OR为3．111（95％CI为1．422—6．805），携带变异基因的患病风险率高。AHSG＊1、AHSG＊2等位基因频率总体分布差异有显著性（Χ^2=8．723，P=0．003），携带AHSG＊2等位基因患病危险度高，OR为2．561（95％CI为1．358—4．831）。Ⅳ期子宫内膜异位症组在位子宫内膜腺胞芳香酶P450的表达为（2．1±1．2）分，显著高于对照组为（0．9±1．1）分，两组比较，差异有统计学意义（P〈0．01）。Ⅳ期子宫内膜异位症组异位内膜腺胞芳香酶P450的表达为（1．5±1．0）分，显著低于在位子宫内膜组，两组比较，差异有统计学意义（P〈0．05）。结论：AHSG＊2基因可使患Ⅳ期卵巢子宫内膜异位囊肿的遗传易感性升高。子宫内膜异位症患者在位、异位内膜腺细胞芳香酶P450表达增加，可促进异位病灶的生长，表达不同反映了不同类型的子宫内膜异位症组织雌激素调节水平不同。

Objective： To explore the possible association between polymorphism at AHSG gene and stage Ⅳ endometriosis and expression of aromatase P450 in eutopic and ectopic endometrium. Methods： The genetic polymorphism of AHSG were analyzed by polymerase chain reaction （PCR） technique in peripheral blood leukocytes in 50 stage Ⅳ endometfiosis （ovary chocolate cysts） and 62 non -endometfiosis cases. The expression of aromatase P450 was detected by immunohistochemical analysis for eutopic and ectopic endometrium in 50 Ⅳ endometrlosis patients and 62 controls. Results： Among 50 patients with stage IV endometriosis （ovary chocolate cysts） and 62 controls, the frequency of AHSG 1 ＊ 1, AHSG1 ＊ 2, AHSG2 ＊ 2 was 44% , 46% , 10% and 71% , 25.8% , 3.2% , respectively. Combined gcnotype of AHSG1 ＊ 2 and AHSG2 ＊ 2, then compared it with the wide -type. A statistic difference was found between the two groups. （Χ^2 = 8. 317, P = 0. 004） OR = 3. 111 （95 % CI ： 1. 422 - 6. 805 ） . Statistic analysis suggested AHSG genotype polymorphism increased risk of stage IV endometriosis （ ovary chocolate cysts） . AHSG ＊ 1, AHSG ＊ 2 alleles differed significantly between the two groups （Χ^2 = 8. 723, P = 0. 003 ） with OR = 2. 561, （95 % CI： 1. 358 - 4. 831 ）, which suggested that AHSG ＊ 2 allele increased risk of stage IV endometriosis （ ovary chocolate cysts） . Expression of aromatase P450 in eutopic endometrium in stage IV endometdosis （ histochemistry score 2. 1 ± 1.2） was significantly higher than that in control group （ 0. 9 ±1.1 ） （ P 〈0.01 ） . Expression of aromatase P450 in ectopic endometrium in stage IV endometriosis （ histochemistry score 1.5 ± 1. 0） was signiftcenfly lower than that in eutopic endometriurn （ P 〈0. 05） . Conclusion： AHSG polymorphism is highly associated with the genetic susceptibility to stage IV endometriosis. The increased expression of aromatase P450 in eutopic and ectopic endometrium in stage IV endometriosis can promote the growth and implantation of endometriosis.