The association of polymorphism in dioxin related genes with leiomyoma and endometriosis

二恶英相关基因多态性与子宫肌瘤、子宫内膜异位症的关系

• 批准号: 14571582
• 负责人: ASADA Hironori
• 金额: $ 1.79万
• 依托单位: KEIO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571582/
• 关键词: dioxin; leiomyoma; endometriosis

Estrogen dependence and immune modulations are established features of endometriosis, and environmental contaminants have been suggested to play a role in the pathobiology of endometriosis. Previous work in nonhuman primates has shown that exposure to the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with an increased prevalence and severity of endometriosis. The effects of dioxins are mediated via the arylhydrocarbon receptor(AHR), aryl hydrocarbon receptor nuclear receptor nuclear translocator(ARNT), and aryl hydrocarbon receptor repressor(AHRR).We identified and characterized the human homolog of mouse AHRR, taking advantage of the publicly available draft version of the human genome sequence. After detecting the AHRR polymorphism, the genetic polymorphism of AHR, ARNT were also investigated. We explored the association of the AHR, ARNT, and AHRR polymorphism with endometriosis in a case-control study. Although no significant correlation was found between endometriosis and polymorphism of AHR, ARNT, or AHRR genes, pathological phenotypes of endometriosis may be associated with the dioxin related genes other than AHR, ARNT, and AHRR.

雌激素依赖和免疫调节是子宫内膜异位症的既定特征，环境污染物被认为在子宫内膜异位症的病理生物学中起作用。以前在非人类灵长类动物中的研究表明，接触二恶英2，3，7，8-四氯二苯并-对二恶英(TCDD)与子宫内膜异位症的患病率和严重程度有关。二恶英的作用是通过芳烃受体(AHR)、芳烃受体核受体核转位蛋白(ARNT)和芳烃受体阻滞剂(AHRR)介导的。我们利用公开可用的人类基因组序列草案版本，鉴定和鉴定了小鼠AHRR的人类同源物。在检测AHRR基因多态性后，还对AHR、ARNT基因的遗传多态性进行了研究。在一项病例对照研究中，我们探讨了AHR、ARNT和AHRR基因多态性与子宫内膜异位症的关系。虽然AHR、ARNT、AHRR基因多态性与子宫内膜异位症无明显相关性，但其病理表型可能与AHR、ARNT、AHRR以外的二恶英相关基因有关。

项目成果

Maruyama T, Yamamoto Y, Shimizu A, Masuda H, Sakai N, Sakurai R, Asada H, Yoshimura Y: "Pyrazolo pyrimidine-type inhibitors of src family tyrosine kinases promote ovarian steroid-induced differentiation of human endometrial stromal cells In Vitro."Biol Re

Maruyama T、Yamamoto Y、Shimizu A、Masuda H、Sakai N、Sakurai R、Asada H、Yoshimura Y：“src 家族酪氨酸激酶的吡唑并嘧啶型抑制剂可促进卵巢类固醇诱导的人子宫内膜基质细胞体外分化。”

Akahoshi K, Sakazume S, Kosaki K, Ohashi H, Fukushima Y: "EEC syndrome type 3 with a heterozygous germline mutation in the P63 gene and B cell lymphoma."Am J Med Genet.. 120A(3). 370-373 (2003)

Akahoshi K、Sakazume S、Kosaki K、Ohashi H、Fukushima Y：“EEC 综合征 3 型，P63 基因杂合种系突变和 B 细胞淋巴瘤。”Am J Med Genet.. 120A(3)。

Kosaki K, Suzuki T, Muroya K, Hasegawa T, Sato S, Matsuo N, Kosaki R, Nagai T, Hasegawa Y, Ogata T: "PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome."J Clin Endocrinol Metab.. 87(8). 352

小崎 K、铃木 T、Muroya K、长谷川 T、佐藤 S、松尾 N、小崎 R、永井 T、长谷川 Y、绪方 T：“7 名日本 Noonan 患者的 PTPN11（蛋白酪氨酸磷酸酶，非受体型 11）突变

Asada H, Kishi I, Kaseda S, Nakagawa H, Maruyama T, Yoshimura Y: "Laparoscopic treatment of polycystic ovaries with the Holmium : YAG laser"Fertil Steril. 4(77). 852-853 (2002)

Asada H、Kishi I、Kaseda S、Nakakawa H、Maruyama T、Yoshimura Y：“用钬：YAG 激光腹腔镜治疗多囊卵巢”Fertil Steril。

Shiokawa S, Iwashita M, Akimoto Y, Nagamathu S, Sakai K, Hamashi H, Kabir-Salmani M, Nakamura Y, Uehata M, Yoshimura Y: "Small guanosine triphospatase RhoA and Rho-associated kinase as regulators of trophoblast migration"J Clin Endocrinol Metab. 87. 5808-

Shiokawa S、Iwashita M、Akimoto Y、Nagamathu S、Sakai K、Hamashi H、Kabir-Salmani M、Nakamura Y、Uehata M、Yoshimura Y：“小鸟苷三磷酸酶 RhoA 和 Rho 相关激酶作为滋养层迁移的调节剂”J Clin