Impact of genes related to immune tolerance and inflammation (tumour necrosis factor-α, interleukin-6) on blood pressure, protein excretion and oedema in pregnancy

Pfab, Thiemo; Chen, You‐Peng; Slowinski, Torsten; Richter, Claus M; Godes, Michael; Arck, Petra C.; Halle, H; Hocher, Berthold

doi:10.1097/01.hjh.0000188732.52722.5a

Cited by 25 publications

(20 citation statements)

References 24 publications

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“…Although considerable efforts have been made in recent years to identify the genes responsible for the development of preeclampsia, and many genes have been identified, including angiotensinogen (5), the type 1 and type 2 angiotensin receptors (6,7), tumor necrosis factor a (8), endothelial nitric oxide synthase (9), methylene tetrahydrofolate reductase (10), and the Leiden variant of coagulation factor V (11), the results have not been consistently reproducible. Recent two studies in a large population suggested that polymorphisms of angiotensinogen gene and immune tolerance and inflamation related genes (tumour necrosis factor-a and interlenkin-6) might play a role in pathogenesis of gestational hypertension and preeclampsia (12,13),supporting some of the above findings.…”

Section: Introductionmentioning

confidence: 66%

The C825T Polymorphism in the G-protein Beta 3 Subunit Gene in Chinese Patients with Preeclampsia

Liu²,

Fan³

et al. 2009

Hypertension in Pregnancy

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Section: Introductionmentioning

confidence: 66%

The C825T Polymorphism in the G-protein Beta 3 Subunit Gene in Chinese Patients with Preeclampsia

Liu²,

Fan³

et al. 2009

Hypertension in Pregnancy

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“…We have seen evidence that preeclamptic women with the TNF-α 308A genotype exhibit higher blood pressure and urinary protein excretion. This may play an important role in the etiology of gestational hypertension and PE [36,37]. Furthermore, severe IUGR-complicated PE was observed more frequently in carriers of the rs1800629 allele A [35].…”

Section: Discussionmentioning

confidence: 99%

“…The resulting outcome is variable clinical phenotypes, e.g. increased proteinuria, fetal growth restriction, severe PE or preterm labor [36,37,64,65]. …”

Section: Discussionmentioning

confidence: 99%

“…However, the A allele was shown to be functionally important, which may play some role in clinically directed management of preeclamptic women. Carriers of this allele, compared with the groups homozygous for the G allele, may exhibit higher values of maternal blood pressure and proteinuria in the third trimester [36,37] or IUGR-complicated PE [35]. Unfortunately, there is only one follow-up study, with contradictory results, which aimed to assess the link between the TNF-α G308A gene polymorphism and incidence of fetal growth retardation, preterm delivery and PE [31].…”

Section: Introductionmentioning

confidence: 99%

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TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Žúbor

Dokus²,

Zigo³

et al. 2014

Gynecol Obstet Invest

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Background/Aims: Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance. The role of tumor necrosis factor-α (TNF-α), a cytokine involved in inflammation processes, has been widely investigated in obstetric disorders. The aims of the present study were to investigate the effect of TNF-α gene G308A (rs1800629) polymorphism on disease risk, renal function, microvascular permeability, endothelial cell dysfunction and organ involvement in women with PE. Methods: Initially, 102 3rd-trimester pregnant women (preeclamptic cases and healthy controls) with singleton pregnancy were invited for participation, of which 76 were genotyped for TNF-α G308A polymorphism and evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), fibronectin and TNF-α, which were tested for correlations with the profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to test the association between the TNF-α polymorphism and PE risk. For continuous variables, we applied Student's t test and, for categorical variables, the Pearson χ² or Fisher's exact test. The two-way ANOVA test with Bonferroni correction was used in multivariate analyses. Results: The A allele was more frequent in cases than controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal serum levels of TNF-α, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/ml, 1,243 ± 671 ng/ml, 0.308 ± 0.231 g/l, respectively) compared to controls (301.1 ± 156.1 pg/ml, 651 ± 250 ng/ml, 0.218 ± 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031, respectively), and these levels showed an increasing trend with the mutant allele genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p < 0.01), respectively). The adverse effect of rs1800629 allele A on renal function was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.

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“…21,22 As a single polymorphism most probably accounts only for a small part of the multifactorial pathogenesis of hypertensive disorders of pregnancy, it may be hard to detect its effect when focusing on binary end points such as gestational hypertension or preeclampsia. In contrast, the analysis of markers such as blood pressure (BP) elevation, protein excretion and oedema during pregnancy might be able to detect small but significant genetic effects.…”

Section: Introductionmentioning

confidence: 99%

Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy

Hocher

Hügle

et al. 2008

J Hum Hypertens

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A genetic association study was conducted to assess whether genetically determined alterations of the nitric oxide system are associated with clinical markers of preeclampsia. A large number of Caucasian women were consecutively included after delivery and genotyped for the endothelial nitric oxide synthase gene (NOS3) polymorphisms G894T, T789C (n ¼ 1502) and intron 4a/b (n ¼ 2186). There are no significant differences in mean blood pressure (BP), protein excretion or new-onset peripheral oedema between any of the genotypes over the course of pregnancy. Neither particular haplotypes nor the combined presence of any two alleles is associated with those markers of pre-eclampsia. The maternal polymorphisms do not seem to influence fetal growth, birth weight or the incidence of congenital malformations. We demonstrate in a large Caucasian population that maternal polymorphisms of the NOS3 gene are not related to clinical markers of pre-eclampsia. The functional relevance of the NOS3 variants alone does not seem to be strong enough to affect BP regulation during pregnancy.

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Impact of genes related to immune tolerance and inflammation (tumour necrosis factor-α, interleukin-6) on blood pressure, protein excretion and oedema in pregnancy

Cited by 25 publications

References 24 publications

The C825T Polymorphism in the G-protein Beta 3 Subunit Gene in Chinese Patients with Preeclampsia

The C825T Polymorphism in the G-protein Beta 3 Subunit Gene in Chinese Patients with Preeclampsia

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy

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