Polymorphisms in the tumor necrosis factor and lymphotoxin-alpha gene region and preeclampsia

OBJECTIVE: To investigate potential association or linkage among nine polym orphisms in the genes encoding tumor necrosis factor (TNF) alpha or lymphot oxin (LT) alpha and preeclampsia. METHODS: Four di-allelic polymorphisms and five microsatellite markers in t he genes encoding TNF-alpha (TNF) and LT alpha (LTA) and their haplotypes w ere studied in 150 Dutch families. These families contained sib-pairs of wo men affected with preeclampsia; eclampsia; the hemolysis, elevated liver en zymes, low platelets (HELLP) syndrome (strict criteria); or pregnancy-induc ed hypertension (mild criteria). Frequencies were compared with 98 healthy controls. Nonparametric affected sib-pair analyses for allele sharing among siblings were carried out for all nine markers. Each sibship was composed of an affected index woman and one or more affected sisters. RESULTS: Although we found a striking association with the TNF-I haplotype in 30 index women with (pre-) eclampsia or HELLP syndrome compared with con trols (odds ratio [OR] 3.8; 95% confidence interval [CI] 1.6, 8.9), this as sociation was not found in their 30 sisters meeting similar disease criteri a. Analyses in all 150 families showed a similar TNF-I association in 122 i ndex women meeting the strict criteria compared with controls (OR 1.9; 95% CI 1.1, 3.3), but, again, not in their 91 sisters meeting similar disease c riteria. This association was stronger in a subgroup of 75 index women with preeclampsia only (OR 2.3; 95% CI 1.2, 4.2). No excess allele sharing for any marker was seen between the siblings. CONCLUSION: The nine polymorphisms studied in the TNF-LTA region did not sh ow evidence for association or linkage with familial preeclampsia. (C) 2001 by the American College of Obstetricians and Gynecologists.