Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetalmembranes

OBJECTIVE: The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated wi th increased gene transcription. In this study we tested the hypothesis tha t this rarer allele is associated with spontaneous preterm birth. STUDY DESIGN: We conducted a case-control study of women admitted to our la bor and delivery unit. To assess data from a single racial group with a hig h incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study per iod. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature ru pture of membranes. Control subjects (n = 110) included women who were deli vered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm prema ture rupture of the fetal membranes (n = 26). RESULTS: Although carriers (homozygotes plus heterozygotes) of the rarer al lele of the polymorphism at position -308 in the gene for tumor necrosis fa ctor cr were not significantly more common among women who were delivered p reterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P=.08 , odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rare r allele were more common among women who were delivered preterm after pret erm premature rupture of membranes (n = 15/26, 58%) than among control subj ects (P=.008, odds ratio 3.18, 95% confidence interval 1.33-7.83). CONCLUSIONS: Our results demonstrate an association between allelic variant s of the polymorphism at position -308 in the gene for tumor necrosis facto r alpha and preterm birth after preterm premature rupture of the fetal memb ranes. We hypothesize that host susceptibility to environmental factors, su ch as hyperresponsiveness of the gene for tumor necrosis factor alpha to ge nital tract infection, may promote preterm premature rupture of the fetal m embranes and subsequent preterm delivery. (Am J Obstet Gynecol 1999;180:129 7-302.).