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Association between polymorphisms in renin-angiotensin system genes and primary ovarian insufficiency in Korean women

Jung, Yong Wook MD1; Jeon, Young Joo MS2,3; Park, Hye Mi MS2,3; Lee, Bo Eun BS2,3; Rah, HyungChul DVM, PhD2,3; Lee, Woo Sik MD, PhD4; Yoon, Tae Ki MD, PhD4; Kim, Nam Keun PhD2,3

doi: 10.1097/gme.0b013e3182733921
Original Articles

Objective The purpose of this study was to evaluate the relationship between angiotensin-converting enzyme (ACE; insertion/deletion), angiotensinogen (AGT M235T), and angiotensin II type 1 receptor (AT1R 1166A>C) and the prevalence of primary ovarian insufficiency (POI) in Korean women.

Methods A total of 133 women with POI and 238 controls were genotyped for polymorphic sites in each gene using polymerase chain reaction–restriction fragment length polymorphism analysis.

Results ACE ID and ID + II variants occurred more frequently in women with POI than in controls (odds ratio [OR], 1.830; 95% CI, 1.040-3.221; P = 0.040; and OR, 1.797; 95% CI, 1.055-3.060; P = 0.031, respectively). The AT1R 1166AC genotype occurred more frequently in participants with POI than in controls (OR, 3.171; 95% CI, 1.562-6.436; P = 0.002). Comparing the combined genotype frequencies of ACE/AT1R revealed that the frequencies of ID/AA, ID/AC, and II/AC were higher in participants than in controls (OR, 1.916; 95% CI, 1.053-3.485; P = 0.043; OR, 3.544; 95% CI, 1.207-10.407; P = 0.036; and OR, 7.875; 95% CI, 2.224-27.881; P = 0.001, respectively). The TT/AC genotype for combined genotyping of AGT/AT1R was more frequently observed in the POI group than in the control group (OR, 3.472; 95% CI, 1.450-8.313; P = 0.006). In multifactor dimensionality reduction–based haplotype analysis, the I-T-C genotype of ACE/AGT/AT1R was a possible predisposing factor for POI (OR, 4.678; 95% CI, 1.721-12.717; P = 0.002).

Conclusions This study demonstrates that polymorphisms in the renin-angiotensin system are related to the prevalence of POI. Thus, these renin-angiotensin system genes may serve as a novel marker for predicting the development of POI.

From the 1Department of Obstetrics and Gynecology, School of Medicine, 2Department of Biomedical Science, College of Life Science, and 3Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea; and 4Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, South Korea.

Received July 18, 2012; revised and accepted September 6, 2012.

Funding/support: This study was partly supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare, and Family Affairs, South Korea (A084923) and partly supported by the Priority Research Centers Program (2009-0093821) and the Basic Science Research Program (2012-007033) through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology, South Korea.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Nam Keun Kim, PhD, Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 351 Yatap-dong, Bundang-gu, Seongnam 463-712, South Korea. E-mail:

© 2013 by The North American Menopause Society.