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Epistasis between polymorphisms in PCSK1 and DBH is associated with premature ovarian failure

Pyun, Jung-A MS1; Kim, Sunshin PhD1; Cha, Dong Hyun MD, PhD2; Kwack, KyuBum PhD1

doi: 10.1097/GME.0000000000000226
Brief Report

Objective: This study examined whether epistasis between single nucleotide polymorphisms (SNPs) within proprotein convertase subtilisin/kexin type 1 (PCSK1) and dopamine β-hydroxylase (DBH) genes is associated with premature ovarian failure (POF).

Methods: One hundred twenty women with POF and 222 female controls were recruited for this study. To genotype SNPs within PCSK1 and DBH, we used a GoldenGate assay with VeraCode technology, which uses an allele-specific primer extension method.

Results: Two SNPs (rs155979 and rs3762986) within PCSK1 and one SNP (rs1611114) within DBH, which were located in the 5′ flanking region, were involved in synergistic interactions. The C allele in the rs155979 SNP showed an increased risk of POF in a dominant model when AA genotype in the rs1611114 SNP was present (odds ratio, 3.60; 95% CI, 1.82-7.14; P = 0.00024), whereas the G allele in the rs1611114 SNP showed a reduced risk of POF in a dominant model when at least one C allele at the rs155979 SNP was present (odds ratio, 0.24; 95% CI, 0.11-0.51; P = 0.00018) or one G allele at the rs3762986 SNP was present (odds ratio, 0.33; 95% CI, 0.19-0.60; P = 0.00023).

Conclusions: Epistases between SNPs within PCSK1 and DBH genes are significantly associated with susceptibility or resistance to POF.

From the 1Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; and 2Division of Genetics, Department of Obstetrics and Gynecology, College of Medicine, CHA General Hospital, CHA University, Seoul, Republic of Korea.

Received November 14, 2013; revised and accepted January 30, 2014.

Funding/support: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2009-0093821, 2011-0010637, and 2013 BK21 PLUS-22A20130012771).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: KyuBum Kwack, PhD, Department of Biomedical Science, College of Life Science, CHA University, 222 Yatap-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-836, Republic of Korea. E-mail:,

© 2014 by The North American Menopause Society.