Article
Impact of genes related to immune tolerance and inflammation (TNF-alpha, IL-6) on blood pressure, protein excretion and edema in pregnancy
Einfluss immuntoleranz- und inflammationsrelevanter Gene (TNF-alpha, IL-6) auf Blutdruck, Proteinausscheidung und Ödeme in der Schwangerschaft
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Published: | August 8, 2006 |
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The objective of the study was to test the hypothesis that genetically determined alterations of maternal immune tolerance to fetal semi-allograft are important for the pathogenesis of hypertensive disorders in pregnancy. A genetic association study was performed to analyse the impact of genetic polymorphisms known to be involved in immune tolerance on markers of preeclampsia such as systolic and diastolic blood pressure, urinary protein excretion and edema. 1480 Caucasian women were consecutively included after delivery at the obstetrics department of the Charité and genotyped for two polymorphisms: tumor necrosis factor (TNF)-alpha -308G>A and interleukin (IL)-6 -174G>C. Only women carrying at least one mutant allele of both polymorphisms (TNF-alpha A and IL-6 C) have a significantly elevated mean systolic and diastolic blood pressure at the end of pregnancy. The TNF-alpha A allele on its own is significantly associated with urinary protein excretion in the last trimenon and the IL-6 C allele is independently and significantly associated with new-onset edema. 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 edema during pregnancy. The analysed polymorphisms seem to contribute to the multifactorial pathogenesis of gestational hypertension and preeclampsia. The findings support the hypothesis that genetically determined factors of maternal immune tolerance play a role in the pathogenesis of hypertensive disorders in pregnancy.