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

Abstract

To investigate potential association or linkage among nine polymorphisms in the genes encoding tumor necrosis factor (TNF) alpha or lymphotoxin (LT) alpha and preeclampsia. Four di-allelic polymorphisms and five microsatellite markers in the genes encoding TNF-alpha (TNF) and LTalpha (LTA) and their haplotypes were studied in 150 Dutch families. These families contained sib-pairs of women affected with preeclampsia; eclampsia; the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (strict criteria); or pregnancy-induced 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. Although we found a striking association with the TNF-I haplotype in 30 index women with (pre-)eclampsia or HELLP syndrome compared with controls (odds ratio [OR] 3.8; 95% confidence interval [CI] 1.6, 8.9), this association was not found in their 30 sisters meeting similar disease criteria. Analyses in all 150 families showed a similar TNF-I association in 122 index 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 criteria. 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. The nine polymorphisms studied in the TNF-LTA region did not show evidence for association or linkage with familial preeclampsia.