Fas (TNFRSF6) gene polymorphism in pregnant women with hemolysis, elevated liver enzymes, and low platelets and in their neonates.

OBJECTIVE

To estimate whether an A>G polymorphism at position -670 in the gene coding for Fas (gene symbol TNFRSF6) is associated with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome.

METHODS

In a retrospective study, buccal swabs from 81 women with the complete form of HELLP syndrome and 83 normotensive control women with uncomplicated full-term pregnancy, and 110 of their neonates, were analyzed for the presence of the TNFRSF6-670 polymorphism. Investigators were blinded to clinical outcomes.

RESULTS

Pregnant women heterozygous for the TNFRSF6-670 genotype were more likely than those homozygous for TNFRSF6-670*A allele to have HELLP syndrome (P = .01; odds ratio 2.7, 95% confidence interval 1.2-5.9). Moreover, patients with homozygous carriage of the TNFRSF6-670*G allele were more likely than those homozygous for the wild type of the Fas gene (TNFRSF6-670*A/A) to have HELLP syndrome (P = .006; odds ratio 4.0, 95% confidence interval 1.7-9.8). In contrast, TNFRSF6-670 genotype distribution of neonates born to mothers with HELLP syndrome was not statistically different from that found in neonates born to healthy pregnant women (P = .4). In patients with HELLP syndrome, no association between TNFRSF6 genotype distribution and severity of hemolysis, platelet counts or liver enzymes levels was noted.

CONCLUSION

A single A>G nucleotide substitution at position -670 in the maternal but not neonatal TNFRSF6 gene coding for Fas is associated with a higher risk for HELLP syndrome.

LEVEL OF EVIDENCE: II-2.