Variants of HSD11B2 gene in hypertensive disorders of pregnancy.
BACKGROUND
One of the hypotheses concerning the etiology of gestational hypertension (GH) and pre-eclampsia (PE) assumes that they develop as a result of placenta malfunctioning at the early stage of pregnancy. Placental dysfunction is also associated with the decreased activity of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which in normal pregnancy protects the fetus from the excess of maternal cortisol.


OBJECTIVE
The aim of the study was to analyze the sequence of HSD11B2, a gene that encodes 11β-HSD2, searching for mutations and haplotypes associated with the increased risk of GH or PE. Those may serve as potential genetic markers of GH and PE.


METHODS
The study was performed in case-control structure and included pregnant women (in third trimester) diagnosed with: GH, PE or being normotensive (control group). The research comprised DNA sequencing of HSD11B2, followed by restriction analysis (PCR-RFLP). The linkage disequilibrium analysis and haplotype-based case-control analysis were performed.


RESULTS
Six sequence variations were observed. Four mutations were indicated in the coding region of HSD11B2 and the other two in 3'-UTR. Two SNPs: c.468C > A and c.534G > A were found to be in total disequilibrium.


CONCLUSIONS
High variability in HSD11B2 sequence was indicated in the study population, but the relevance of observed SNPs to GH or PE development was not confirmed.
a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
Katarzyna
K
Kosicka
a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
Anna
A
Siemiątkowska
a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
Agnieszka
A
Pękal
b Department of Pharmaceutical Biochemistry , Poznan University of Medical Sciences , Poznań , Poland , and.
Aleksandra
A
Majchrzak-Celińska
c Department of Perinatology and Gynecology , Poznan University of Medical Sciences , Poznań , Poland.
Grzegorz
G
Bręborowicz
c Department of Perinatology and Gynecology , Poznan University of Medical Sciences , Poznań , Poland.
Mariola
M
Krzyścin
a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
Franciszek
F
Główka
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics*; D009154:Mutation; D016017:Odds Ratio; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D055815:Young Adult
D005819:Genetic Markers; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human
11β-hydroxysteroid dehydrogenase type 2; Gestational hypertension; cortisol; glucocorticoid; pre-eclampsia