Association of the TNF2 Allele with Eclampsia

Kaiser, Thomas; Grehan, Madonna; Brennecke, Shaun P.; Moses, Eric K.

doi:10.1159/000076689

Cited by 23 publications

(15 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation is in agreement with previous reports [23,24,25,28,29,30], but contradicts other reports that showed no linkage between the A allele and PE development [19,20,21,22,26,27,33,34,35]. The explanation could be the genetic variability among ethnic populations and that certain polymorphisms may be more prevalent in some ethnic groups.…”

Section: Discussionsupporting

confidence: 90%

“…A Medline search using the keywords ‘TNF-α polymorphism' and ‘preeclampsia' yielded a total of 19 papers. The majority evaluated the genotype and allele frequencies with/without disease risk estimation [19,20,21,22,23,24,25,26,27,28,29,30,31,32] and showed, after three meta-analyses covering over 2,300 cases and 1,900 controls [33,34,35], that there is no significant impact of this SNP on PE risk. However, the A allele was shown to be functionally important, which may play some role in clinically directed management of preeclamptic women.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…However, the size was sufficient to detect (with an 80% power) a possible association between cytokine gene polymorphism and E/PE, in accordance with earlier studies. 26,27,48 These findings need to be replicated in future studies. The role of these cytokine gene SNPs in PE/E has to be further investigated, because they may be involved with etiology and not with susceptibility to disease.…”

Section: Discussionmentioning

confidence: 91%

“…Sample size estimates were based on a reported 67% frequency of TNF-a (308G) in the general population and a 43% frequency of TNF-a (À308G) in patients with increased susceptibility to E. 26 Assuming a similar difference in TNF-a (À308G) frequencies between patients and controls, a two-tailed-a of 0.05 and 80% power, a sample size of 67 per group would be sufficient to detect an association between this allele and E/PE. We selected this specific TNF-a SNP for sample size calculation as it is the most frequently assessed in PE studies.…”

Section: Discussionmentioning

confidence: 99%

“…We selected this specific TNF-a SNP for sample size calculation as it is the most frequently assessed in PE studies. [12][13][14]26,27 Hardy-Weinberg equilibrium tests were carried out by calculating the expected frequencies of each genotype and comparing them with the observed values. Arlequin software (Geneva, Switzerland) was used for these analyses.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytokine gene polymorphisms in preeclampsia and eclampsia

Lima¹,

Sass

Mattar

et al. 2009

Hypertens Res

View full text Add to dashboard Cite

The clinical spectrum of preeclampsia (PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. The biological factors that determine the progression of PE to eclampsia (E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. The production of cytokines, IL-10 and TGF-b1, is apparently suppressed, and altered IL-2/IL-10 and TNF-a/IL-10 ratios have been reported in preeclamptic cases. The relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-a promoter (À308 G4A), IL6 promoter (À174 G4C), IFN-c intron 1 (+874 A4T), IL10 promoters (À1082 A4G), (À819 C4T) and (À592 C4A) and TGF-b1 codon 10 (+869 T4C) and codon 25 (+915 G4C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. The v 2 or Fisher's exact tests were used to compare genotype frequencies. Among the six singlenucleotide polymorphisms (SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-c (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P¼0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil.

show abstract