title: Epistasis between polymorphisms in PCSK1 and DBH is associated with premature ovarian failure.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Pyun
authors.forename: Sunshin
authors.initials: S
authors.lastname: Kim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Cha
authors.forename: KyuBum
authors.initials: K
authors.lastname: Kwack
mesh_terms: D000328:Adult; D000483:Alleles; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D045664:Proprotein Convertase 1 / Q000235:genetics*
chemical_list: D004299:Dopamine beta-Hydroxylase; C587576:PCSK1 protein, human; D045664:Proprotein Convertase 1