POLYMORPHISMS OF IMMUNE-RELATED GENES ASSOCIATED WITH PATHOGENESIS OF ENDOMETRIOSIS

• Project/Area Number: 15591772
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
• Principal Investigator: KITAWAKI Jo Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Associate Professor, 医学研究科, 助教授 (00204925)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: ENDOMETRIOSIS / POLYMORPHISMS / CYTOKINES / TNF-α / INTERFERON-γ / HLA

Research Abstract

Endometriosis is defined by the presence of endometrium-like lesions outside the uterine cavity. Although the exact etiology and pathogenesis are unclear, genetic, endocrine, immune, and environment factors have been implicated in the disease. Familial and twin studies have indicated 5-8% increase in risk for first-degree relatives, suggesting that endometriosis is a genetic disorder with polygenic or multifactorial inheritance. Studies have implied a role for genetic factors in the association between the development of endometriosis and genetic polymorphisms.
Defects in the ability of cytotoxic T cells and natural killer (NK) cells to recognize and lyse ectopic endometrial cells are considered crucial for disease pathogenesis. NK cells recognize specifically the HLA class I molecules that inhibit the killing functions of these T cells. In the present study, we found that the HLA-A24-B^*0702-Cw^*0702-DRB1^*0101 haplotype and polymorphisms in the TNF-α gene promoter and interferon-γ gene are possible genetic susceptibility factors. Interleukin-10 gene promoter polymorphism is associated with production of anti-carbonic anhydrase II autoantibodies in patients with endometriosis.

Research Products

• [Journal Article] Aromatase cytochrome P450 and estrogen and progesterone receptors in uterine sarcomas : correlation with clinical parameters (2004)
  • Author(s): Kitaoka Y, Kitawaki J, Koshiba H, Inoue S, Ishihara H, Teramoto M, Honjo H
  • Journal Title: Journal of Steroid Biochemistry and Molecular Biology 88 Pages: 183-189
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Interferon-γ gene dinucleotide (CA) repeat and interleukin-4 promoter region (-590C/T) polymorphisms in Japanese patients with endometriosis (2004)
  • Author(s): Kitawaki J, Koshiba H, Kitaoka Y, Teramoto M, Hasegawa G, Nakamura N, Yoshikawa T, Ohta M, Obayashi H, Honjo H
  • Journal Title: Human Reproduction 19 Pages: 1765-1769
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic contribution of tumor necrosis factor (TNF)-α gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility (2004)
  • Author(s): Teramoto M, Kitawaki J, Koshiba H, Kitaoka Y, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Matsushita M, Maruya E, Saji H, Ohta M, Honjo H
  • Journal Title: American Journal of Reproductive Immunology 51 Pages: 352-357
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis : possible association with progression of endometriosis (2004)
  • Author(s): Koshiba H, Kitawaki J, Teramoto M, Kitaoka Y, Ishihara H, Obayashi H, Ohta M, Hara H, Adachi T, Honjo H
  • Journal Title: Journal of Clinical Endocrinology and Metabolism 90 Pages: 529-537
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic contribution of tumor necrosis factor (TNF) -α gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility (2004)
  • Author(s): Teramoto M, Kitawaki J, Koshiba H, Kitaoka Y, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Matsushita M, Maruya E, Saji H, Ohta M, Honjo H
  • Journal Title: American Journal of Reproductive Immunology 51 Pages: 352-357
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Interferon-γ gene dinucleotide (CA) repeat and interleukin-4 promoter region (-590C/T) polymorphisms in Japanese patients with endometriosis (2004)
  • Author(s): Kitawaki_J, Koshiba H, Kitaoka Y, Teramoto M, Hasegawa G, Nakamura N, Yoshikawa T, Onta M, Obayashi H, Honjo H
  • Journal Title: Human Reproduction 19 Pages: 1765-1769
• [Journal Article] Genetic contribution of tumor necrosis factor (TNF)-α gene promoter (-1031,-863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility (2004)
  • Author(s): Teramoto M, Kitawaki J, Koshiba H, Kitaoka Y, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Matsushita M, Maruya E, Saji H, Ohta M, Honjo H
  • Journal Title: American Journal of Reproductive Immunology 51 Pages: 352-357
• [Journal Article] Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non-pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation (2003)
  • Author(s): Kado N, Kitawaki J, Koshiba H, Ishihara H, Kitaoka Y, Teramoto M, Honjo H
  • Journal Title: Human Reproduction 18 Pages: 715-720
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Giant ovarian tumor removed after preoperative drainage, with abdominoplasty. A case report (2003)
  • Author(s): Koshiba H, Kitawaki J, Fujita H, Honjo H, Okumura J
  • Journal Title: Journal of Reproductive Medicine 48 Pages: 652-654
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kado N, Kitawaki J, Koshiba H, Ishihara H, Kitaoka Y, Teramoto M, Honjo H: "Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non-pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation"Human Reproduction. 18. 715-720 (2003)
• [Publications] Koshiba H, Kitawaki J, Fujita H, Honjo H, Okumura J: "Giant ovarian tumor removed after preoperative drainage, with abdominoplasty. A case report"Journal of Reproductive Medicine. 48. 652-654 (2003)
• [Publications] Teramoto M, Kitawaki J, Koshiba H, Kitaoka Y, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Matsushita M, Maruya E, Saji H, Ohta M, Honjo H: "Grenetic contribution of tumor necrosis factor (TNF)-a gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility"Am Journal of Reproductive Immnunology. (In press).
• [Publications] Kitaoka Y.Kitawaki J, Koshiba H, Inoue S.Ishihara H, Teramoto M, Honjo H: "Aromatase cytochrome P450 and estrogen and progesterone receptors in uterine sarcomas : correlation with clinical parameters"Journal of Steroid Biochemistry and Molecular Biology. (In press).