title: Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women.
abstract: 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.
authors.affiliation: 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.
authors.forename: HyungChul
authors.initials: H
authors.lastname: Rah
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.forename: Jung O
authors.initials: JO
authors.lastname: Kim
authors.forename: Sung Han
authors.initials: SH
authors.lastname: Shim
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Choi
authors.forename: Ji Hyang
authors.initials: JH
authors.lastname: Kim
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000328:Adult; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D028884:Karyopherins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D056910:Republic of Korea; D043244:Ribonuclease III / Q000235:genetics*; D020931:ran GTP-Binding Protein / Q000235:genetics*
chemical_list: D028884:Karyopherins; D035683:MicroRNAs; C120587:RAN protein, human; C446511:XPO5 protein, human; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020931:ran GTP-Binding Protein