title: Identification of circulating microRNAs in HNF1A-MODY carriers.
abstract: OBJECTIVE
  HNF1A-MODY is a monogenic form of diabetes caused by mutations in the HNF1A gene. Here we identify, for the first time, HNF1A-MODY-associated microRNAs (miRNAs) that can be detected in the serum of HNF1A-MODY carriers.
  
  
  METHODS
  An miRNA array was carried out in rat INS-1 insulinoma cells inducibly expressing the common human Pro291fsinsC-HNF1A frame shift mutation. Differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of miRNAs in the serum of HNF1A-MODY carriers (n = 31), MODY-negative family members (n = 10) and individuals with type 2 diabetes mellitus (n = 17) was quantified by absolute real-time PCR analysis.
  
  
  RESULTS
  Inducible expression of Pro291fsinsC-HNF1A in INS-1 cells caused a significant upregulation of three miRNAs (miR-103, miR-224, miR-292-3p). The differential expression of two miRNAs (miR-103 and miR-224) was validated in vitro. Strongly elevated levels of miR-103 and miR-224 could be detected in the serum of HNF1A-MODY carriers compared with MODY-negative family controls. Serum levels of miR-103 distinguished HNF1A-MODY carriers from HbA1c-matched individuals with type 2 diabetes mellitus.
  
  
  CONCLUSIONS
  Our study demonstrates that the pathophysiology of HNF1A-MODY is associated with the overexpression of miR-103 and miR-224. Furthermore, our study demonstrates that these miRNAs can be readily detected in the serum of HNF1A-MODY carriers.
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons, Dublin, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Bonner
authors.forename: K C
authors.initials: KC
authors.lastname: Nyhan
authors.forename: S
authors.initials: S
authors.lastname: Bacon
authors.forename: M P
authors.initials: MP
authors.lastname: Kyithar
authors.forename: J
authors.initials: J
authors.lastname: Schmid
authors.forename: C G
authors.initials: CG
authors.lastname: Concannon
authors.forename: I M
authors.initials: IM
authors.lastname: Bray
authors.forename: R L
authors.initials: RL
authors.lastname: Stallings
authors.forename: J H M
authors.initials: JH
authors.lastname: Prehn
authors.forename: M M
authors.initials: MM
authors.lastname: Byrne
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D007340:Insulinoma / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D051822:T Cell Transcription Factor 1 / Q000235:genetics
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D035683:MicroRNAs; D051822:T Cell Transcription Factor 1