title: TNF α G308A gene polymorphism has an impact on renal function, microvascular permeability, organ involvement and severity of preeclampsia.
abstract: OBJECTIVE
  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 χ(2) 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.
  
  
  CONCLUSIONS
  This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.
authors: Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.
authors: Pavol
authors: P
authors: Zubor
authors: Karol
authors: K
authors: Dokus
authors: Imrich
authors: I
authors: Zigo
authors: Maria
authors: M
authors: Skerenova
authors: Rudolf
authors: R
authors: Pullmann
authors: Jan
authors: J
authors: Danko
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002199:Capillary Permeability / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005353:Fibronectins / Q000097:blood; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000652:urine; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics* / Q000652:urine; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011507:Proteinuria / Q000652:urine; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
chemical_list: D005353:Fibronectins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1