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Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women

Rah, HyungChul DVM, PhD; Jeon, Young Joo MS; Lee, Bo Eun BS; Kim, Jung O BS; Shim, Sung Han PhD; Lee, Woo Sik MD, PhD; Choi, Dong Hee MD, PhD; Kim, Ji Hyang MD; Kim, Nam Keun PhD

doi: 10.1097/GME.0b013e3182883907
Original Study

Objective The aim of our study was to investigate whether polymorphisms in microRNA machinery genes are associated with the risk of primary ovarian insufficiency (POI).

Methods We genotyped 136 POI patients and 236 controls among Korean women for nine single nucleotide polymorphisms (SNPs; DROSHA rs6877842 and rs10719; DICER1 rs13078 and rs3742330; RAN rs14035; and XPO5 rs34324334, rs2257082, rs11544382, and rs11077) by polymerase chain reaction–restriction fragment length polymorphism analysis. Differences in genotype frequencies between patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as measures of the strength of the association between genotype and POI.

Results Of the nine SNPs, XPO5 rs34324334 and rs11544382 were monomorphic and were not analyzed further. The XPO5 rs2257082 CT and CT + TT variant genotypes were more frequent in patients (OR, 2.097; 95% CI, 1.207-3.645) than in controls (OR, 2.030; 95% CI, 1.196-3.445). The combined frequencies of XPO5 rs2257082 CT + TT and rs11077 AC + CC genotypes were higher in patients than in controls (OR, 2.526; 95% CI, 1.088-5.865). An association of POI risk with other polymorphisms was not found. A haplotype-based analysis of seven polymorphisms of the microRNA machinery genes for gene-gene interactions suggests that ***ACTA, ***GCCA, ***G*C*, *T*ATTA, and ***ACT* haplotypes (asterisk indicates SNP locus not included; DROSHA rs6877842 and rs10719, DICER1 rs13078 and rs3742330, RAN rs14035, and XPO5 rs2257082 and rs11077 polymorphisms) are associated with higher POI prevalence, and that ***GCTA, ***ACCA, *C*ATTA, and *C*ATT* haplotypes are associated with lower POI prevalence.

Conclusions Our data demonstrate that the XPO5 rs2257082 T variant allele occurs more frequently in POI patients than in controls, suggesting that this allele may be associated with increased POI risk.

From the 1Department of Biomedical Science, College of Life Science, 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 and Fertility Center, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

Received November 4, 2012; revised and accepted January 16, 2013.

Funding/support: This work was 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, and by a grant from the Korea Healthcare Technology R&D Project (A084923), Ministry for Health, Welfare, and Family Affairs, Republic of 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.