A promoter mutation in the tumor necrosis factor alpha gene is not associated with preeclampsia

Preeclampsia is associated with increased plasma concentrations of tumor necrosis factor alpha (TNF alpha) and TNF receptors. A mutation in the promoter region of the TNF alpha gene (TNF T2) has been described which is associated with increased transcription of the gene. Due to the familial predisposition of preeclampsia, we hypothesized that this promoter mutation in the TNF alpha gene may contribute to the genetic etiology of preeclampsia. Our objective was to determine the allele frequency of this mutation in a population with well-characterized preeclampsia and with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as compared with normotensive controls. DNA was extracted from blood of 131 women with severe preeclampsia, 75 women with HELLP syndrome, and 41 normotensive gravid controls. Genotypes were determined using the polymerase chain reaction (PCR), allele-specific restriction with Nco1, and agarose gel electrophoresis. Results were analyzed with a chi 2 contingency table. No significant differences were found between patients with severe preeclampsia, HELLP syndrome, normotensive gravid controls, and previously published allele frequencies. The frequency of the TNF T2 allele is not increased in patients with preeclampsia or HELLP syndrome. Therefore, this promoter mutation is probably not a major genetic cause of preeclampsia. As more genes are cloned, sequenced and localized, this will enable investigators to take this 'candidate gene approach' to investigate potential genetic causes of preeclampsia.