Impact of genes related to immune tolerance and inflammation (tumour necrosis factor-α, 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. Design 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. Setting The study was conducted at the Obstetrics Department of the Charite University Hospital, Berlin, Germany. Participants 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. Main outcome measures 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.