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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.

Author Information

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.