title: HNF-1alpha G574S is a functional variant with decreased transactivation activity.
abstract: OBJECTIVE
  To assess the functional consequence of the hepatocyte nuclear factor 1alpha gene (HNF-1alpha) G574S variant previously proposed as a diabetes susceptibility allele, in a group of Mexican Type 2 diabetic patients with end-stage renal disease (ESRD).
  
  
  METHODS
  The transcriptional activity of the HNF-1alpha G574S recombinant protein on the human insulin promoter was assessed by transfection assays in RINm5f and HepG2 cell lines.
  
  
  RESULTS
  Two unrelated Mexican diabetic patients with no known African ancestry were found to carry the G574S variant. This substitution was not found among unrelated healthy control subjects. Whereas the G574S HNF-1alpha transcription activation of the human insulin promoter was 40% lower than that of the wild-type protein in RINm5f beta cells, no difference was found in a hepatic cell line (HepG2).
  
  
  CONCLUSIONS
  G574S affects the transactivation potential of HNF-1alpha on the insulin promoter in pancreatic beta-cells. Although it has been difficult to prove its role in the development of diabetes in case-control association studies, this variant exhibits functional effects consistent with it being a potential diabetes susceptibility allele.
authors.affiliation: Instituto Politécnico Nacional Escuela Superior de Medicins, Sección de Estudios de Postgrado e Investigación, Plan de San Luis y Díaz Mirón s/n, Miguel Hidalgo, Mexico.
authors.forename: K
authors.initials: K
authors.lastname: Navalón-García
authors.forename: L
authors.initials: L
authors.lastname: Mendoza-Alcantar
authors.forename: M E
authors.initials: ME
authors.lastname: Díaz-Vargas
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez-Godínez
authors.forename: H
authors.initials: H
authors.lastname: Reyna-Garfias
authors.forename: C A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: L
authors.initials: L
authors.lastname: Riba
authors.forename: S
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.forename: T
authors.initials: T
authors.lastname: Villarreal-Molina
authors.forename: A
authors.initials: A
authors.lastname: González-Chávez
authors.forename: V
authors.initials: V
authors.lastname: Argueta-Villamar
authors.forename: M T
authors.initials: MT
authors.lastname: Tusié-Luna
authors.forename: A
authors.initials: A
authors.lastname: Miliar-García
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D015534:Trans-Activators