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Association between kinase insert domain-containing receptor polymorphisms (−604T>C, 1192G>A, 1719A>T) and premature ovarian failure in Korean women

Rah, HyungChul DVM, PhD1,2; Jeon, Young Joo MS1,2; Choi, Youngsok PhD1,3; Shim, Sung Han PhD1,3; Ko, Jung Jae PhD1; Yoon, Tae Ki MD, PhD3; Cha, Sun Hee MD, PhD4; Kim, Nam Keun PhD1,2

doi: 10.1097/gme.0b013e318248f2e8
Original Articles

Objective: The aim of the study was to investigate whether the −604T>C, 1192G>A, and 1719A>T polymorphisms in the kinase insert domain-containing receptor (KDR) gene confer risk for premature ovarian failure (POF) in Korean women.

Methods: DNA samples from 133 POF patients and 230 controls were genotyped for the three KDR single nucleotide polymorphisms by polymerase chain reaction–restriction fragment length polymorphism analysis.

Results: The POF patients had significantly increased frequencies of the KDR −604TC and −604TC + CC genotypes (odds ratio [OR], 1.975; 95% CI, 1.219-3.201 and OR, 1.948; 95% CI, 1.221-3.109, respectively) and of the −604TC + CC/1192GG combined genotype (OR, 2.271; 95% CI, 1.359-3.795) and a decreased frequency of the 1192GA genotype (OR, 0.457; 95% CI, 0.231-0.905) compared with the controls. The genotype frequency of the 1719A>T polymorphism was not significantly different between the two groups. The frequencies of the KDR −604C/1192G/1719T, −604C/1192G, and −604C/1719T haplotypes (OR, 3.319; 95% CI, 1.564-7.041; OR, 2.083; 95% CI, 1.351-3.212; and OR, 1.979; 95% CI, 1.073-3.649, respectively) were significantly higher among POF patients than controls, whereas the −604T/1719T haplotype frequency (OR, 0.657; 95% CI, 0.472-0.915) was lower among POF patients.

Conclusions: Carriers of the KDR −604C variant allele (−604TC and −604TC + CC genotypes; −604TC + CC/1192GG combined genotype; −604C/1192G/1719T haplotype, −604C/1192G haplotype, −604C/1719T haplotype) are consistently more prevalent among POF patients than among controls, suggesting that the KDR −604C allele may increase the risk of POF development in Korean women.

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

Received November 6, 2011; revised and accepted December 29, 2011.

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

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:

©2012The North American Menopause Society