title: Association of breast cancer-related microRNA polymorphisms with idiopathic primary ovarian insufficiency.
abstract: OBJECTIVE
  The aim of our study was to investigate whether breast cancer-related microRNA polymorphisms are associated with primary ovarian insufficiency (POI) risk.
  
  
  METHODS
  Four breast cancer-related microRNA polymorphisms (miR-27aA > G [rs895819], miR-135bC > T [rs74141216], miR-423C > A [rs6505162], and miR-608G > C [rs4919510]) were genotyped in 136 women with idiopathic POI and 224 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis. Differences in genotype frequencies between cases and controls were compared. Odds ratios and 95% CIs were determined as measures of the strength of association between genotype and POI.
  
  
  RESULTS
  Two haplotypes (G-C-A-G and A-T-C-C) of miR-27a/miR-135b/miR-423/miR-608 were associated with increased POI risk. The haplotypes G-A-G of miR-27a/miR-423/miR-608 and A-T-C of miR-27a/miR-135b/miR-608 were associated with higher POI risk, whereas the G-T haplotype of miR-27a/miR-135b was associated with decreased POI risk. The association between POI risk and the G-A-G haplotype of miR-27a/miR-423/miR-608 remained significant after false discovery rate correction for multiple comparisons. The combined genotypes AA/CT/CC/CC, AG/CC/CA/GC, GG/CC/CC/CC, and GG/CC/CA/GG of miR-27a/miR-135b/miR-423/miR-608 were also associated with higher POI risk. Increased POI risk was observed in combined genotypes GG/CC/GG of miR-27a/miR-135b/miR-608; AA/CC/GC, AG/CA/GC, GG/CC/GG, GG/CC/CC, and GG/CA/GG of miR-27a/miR-423/miR-608; and GG/GG of miR-27a/miR-608; however, these associations were not significant after false discovery rate correction. None of the four microRNA polymorphisms alone was associated with POI risk.
  
  
  CONCLUSIONS
  Our data suggest that breast cancer-related microRNA polymorphisms, including miR-27aA > G, miR-423C > A, and miR-608G > C, are associated with increased POI risk via interactions between miR-27aG, miR-423A, and miR-608G variants. However, our results should be interpreted cautiously because of our small sample size and the low statistical power of our study design.
authors.affiliation: 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; 3Department of Obstetrics and Gynecology and Fertility Center of CHA Bundang Medical Center, CHA University, Seongnam, South Korea; and 4Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, South Korea.
authors.forename: HyungChul
authors.initials: H
authors.lastname: Rah
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Cha
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Kim
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Jung Jae
authors.initials: JJ
authors.lastname: Ko
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D004967:Estrogens / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D004967:Estrogens; C544965:MIRN135 microRNA, human; C531388:MIRN27 microRNA, human; C548900:MIRN423 microRNA, human; C000591804:MIRN608 microRNA, human; D035683:MicroRNAs; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone