Impact of genes related to immune tolerance and inflammation (tumour necrosis factor-alpha, interleukin-6) on blood pressure, protein excretion and oedema in pregnancy.
OBJECTIVE
To test the hypothesis that genetically determined alterations of maternal immune tolerance to a foetal semi-allograft are important for the pathogenesis of hypertensive disorders in pregnancy.


METHODS
A genetic association study was performed to analyse the impact of genetic polymorphisms known to be involved in immune tolerance on markers of pre-eclampsia.


METHODS
The study was conducted at the Obstetrics Department of the Charité University Hospital, Berlin, Germany.


METHODS
A total of 1480 Caucasian women were consecutively included after delivery and genotyped for two polymorphisms: tumour necrosis factor-alpha -308G>A and interleukin-6 -174G>C.


METHODS
Systolic and diastolic blood pressures, urinary protein excretion and oedema during pregnancy.


RESULTS
Only women carrying at least one mutant allele of both polymorphisms (tumour necrosis factor-alpha A and interleukin-6 C) have a significantly elevated mean systolic blood pressure and diastolic blood pressure at the end of pregnancy. The tumour necrosis factor-alpha A allele on its own is significantly associated with urinary protein excretion in the last trimenon, and the interleukin-6 C allele is independently and significantly associated with new-onset oedema.


CONCLUSIONS
We demonstrate in a large population that common maternal polymorphisms of genes related to immune tolerance and inflammation are associated with blood pressure regulation, urinary protein excretion and oedema during pregnancy. The analysed polymorphisms seem to contribute to the multifactorial pathogenesis of gestational hypertension and pre-eclampsia. The findings support the hypothesis that genetically determined factors of maternal immune tolerance play a role in the pathogenesis of hypertensive disorders in pregnancy.
Pfab
Thiemo
T
Center for Cardiovascular Research/Institute of Pharmacology, Charité Mitte, Berlin, Germany.
Chen
You-Peng
YP
Slowinski
Torsten
T
Richter
Claus M
CM
Godes
Michael
M
Arck
Petra C
PC
Halle
Horst
H
Hocher
Berthold
B
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics; D004487:Edema / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007231:Infant, Newborn; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy / Q000235:genetics* / Q000276:immunology*; D011507:Proteinuria / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004247:DNA