title: Non-synonymous sequence variants within the oxygen-dependent degradation domain of the HIF1A gene are not associated with pre-eclampsia in the Finnish population.
abstract: BACKGROUND
  Reduced placental perfusion predisposes to the maternal syndrome pre-eclampsia characterized by systemically reduced perfusion. Considerable data support the role of angiogenic factors in the development of the maternal syndrome. Hypoxia-inducible factor (HIF-1) mediates the cellular responses to hypoxia e.g. by promoting angiogenesis.
  
  
  METHODS
  Here we studied whether two single nucleotide sequence variants, c.1744 C>T that changes residue 582 of HIF-1alpha from proline to serine (P582S) and c.1762 G>A that changes residue 588 of HIF-1alpha from alanine to threonine (A588T) in the exon 12 of the HIF1A gene, are associated with pre-eclampsia. We studied 108 women with pre-eclampsia in their first pregnancy, and 101 controls with normotensive pregnancies. Pre-eclampsia was defined as a blood pressure level of at least 140/90 mmHg in a woman who was normotensive before 20 weeks of gestation, and proteinuria at least of 0.3 g per 24-hour urine collection. The patients and controls were genotyped for variations in the exon 12 of HIF1A gene by sequencing
  
  
  RESULTS
  The frequencies of the c.1744 C>T and c.1762G>A sequence variants were not significantly different between women with pre-eclamptic first pregnancies and women with normotensive pregnancies. In addition, two synonymous variants (c.1740G>A and c.1800A>T) were detected at comparable levels in the two groups. All variants were identified in the heterozygous form.
  
  
  CONCLUSIONS
  The sequence variants in the exon 12 of the HIF1A gene were not associated with pre-eclampsia in the Finnish population.
authors.affiliation: Department of Medical Genetics, Haartman Institute, FI-00014 University of Helsinki, Finland. sanna.heino@helsinki.fi
authors.forename: Sanna
authors.initials: S
authors.lastname: Heino
authors.forename: Milja
authors.initials: M
authors.lastname: Kaare
authors.forename: Sture
authors.initials: S
authors.lastname: Andersson
authors.forename: Hannele
authors.initials: H
authors.lastname: Laivuori
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D005091:Exons; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen