Chia-Lung Tsai1, Yun-Shien Lee2, Angel Chao3, Chih-Feng Yen4, Hsin-Shih Wang4, Tzu-Hao Wang5. 1. Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 2. Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan. 3. Department of Obstetrics and Gynecology, LinKou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Linkou, Taiwan; Gynecologic Cancer Research Centre, LinKou Medical Center, Chang Gung Memorial Hospital, Linkou, Taiwan. 4. Department of Obstetrics and Gynecology, LinKou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Linkou, Taiwan. 5. Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Obstetrics and Gynecology, LinKou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Linkou, Taiwan; Graduate Institutes of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: knoxtn@cgmh.org.tw.
Abstract
OBJECTIVE: We have recently reported that stress-induced phosphoprotein 1 (STIP1) is over-expressed in endometriosis/adenomyosis tissues. STIP1 may also be involved in immune regulation, thus we attempted to study the association between STIP1 single nucleotide polymorphisms (SNPs) and endometriosis/adenomyosis. MATERIALS AND METHODS: Five STIP1 SNPs (rs7941773, rs2845597, rs4980524, rs2282490, and rs2236647) were selected for genotyping with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 286 patients with endometriosis/adenomyosis and 288 healthy postmenopausal controls. In vitro studies included luciferase promoter reporter assays and western blot analysis for STIP1 and MMP9 proteins. RESULTS: The frequency of the G allele at rs4980524 was significantly higher in patients with endometriosis/adenomyosis than in control women. The promoter reporter with rs4980524 GG genotype significantly increased luciferase activity than that with TT genotype in endometrial cancer RL95-2 cells, and the primary endometrial stromal cells carrying rs4980524 GG genotype expressed higher protein levels of STIP1 and MMP9 than those carrying the TT one. CONCLUSION: The G/G allele of STIP1 SNP rs4980524 is associated with the increased expression of STIP1 and MMP9 in endometriosis. Further validation in independent cohorts of endometriosis patients may prove its usefulness as a genetic risk maker for endometriosis/adenomyosis.
OBJECTIVE: We have recently reported that stress-induced phosphoprotein 1 (STIP1) is over-expressed in endometriosis/adenomyosis tissues. STIP1 may also be involved in immune regulation, thus we attempted to study the association between STIP1 single nucleotide polymorphisms (SNPs) and endometriosis/adenomyosis. MATERIALS AND METHODS: Five STIP1 SNPs (rs7941773, rs2845597, rs4980524, rs2282490, and rs2236647) were selected for genotyping with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 286 patients with endometriosis/adenomyosis and 288 healthy postmenopausal controls. In vitro studies included luciferase promoter reporter assays and western blot analysis for STIP1 and MMP9 proteins. RESULTS: The frequency of the G allele at rs4980524 was significantly higher in patients with endometriosis/adenomyosis than in control women. The promoter reporter with rs4980524 GG genotype significantly increased luciferase activity than that with TT genotype in endometrial cancer RL95-2 cells, and the primary endometrial stromal cells carrying rs4980524 GG genotype expressed higher protein levels of STIP1 and MMP9 than those carrying the TT one. CONCLUSION: The G/G allele of STIP1 SNP rs4980524 is associated with the increased expression of STIP1 and MMP9 in endometriosis. Further validation in independent cohorts of endometriosispatients may prove its usefulness as a genetic risk maker for endometriosis/adenomyosis.