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Fas (TNFRSF6) Gene Polymorphism in Pregnant Women With Hemolysis, Elevated Liver Enzymes, and Low Platelets and in Their Neonates

From the ¹First Department of Obstetrics and Gynecology, Semmelweis University Faculty of Medicine, Budapest, Hungary; and ²Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, New York.

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