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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