Research article

Non-synonymous sequence variants within the oxygen-dependent degradation domain of the HIF1A gene are not associated with pre-eclampsia in the Finnish population

Sanna Heino¹ , Milja Kaare² , Sture Andersson^3,4 and Hannele Laivuori^1,5

¹  Department of Medical Genetics, Haartman Institute, FI-00014 University of Helsinki, Finland

²  Folkhälsan Institute of Genetics, FI-00014 University of Helsinki, Finland

³  Hospital for Children and Adolescents, Helsinki University Central Hospital, FI-00029 Finland

⁴  Department of Pediatrics, FI-00014 University of Helsinki, Finland

⁵  Department of Clinical Genetics, Helsinki University Central Hospital, FI-00029 HUS, Finland

author email corresponding author email

BMC Medical Genetics 2008, 9:96doi:10.1186/1471-2350-9-96

Published:	3 November 2008

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-1α from proline to serine (P582S) and c.1762 G>A that changes residue 588 of HIF-1α 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.

Conclusion

The sequence variants in the exon 12 of the HIF1A gene were not associated with pre-eclampsia in the Finnish population.