Association of polymorphism within the promoter of the tumor necrosis factor α gene with increased risk of preterm premature rupture of the fetal membranes

TLDR

A polymorphism at position –308 in the TNF‑α promoter increases gene transcription. The study tested whether this rarer allele is associated with spontaneous preterm birth. A case‑control study of 55 African American women who delivered preterm and 110 controls who delivered after 37 weeks, with subgroup analyses of idiopathic preterm labor and preterm premature rupture of membranes, was conducted. Carriers of the rarer allele were significantly more common among women who delivered preterm after preterm premature rupture of membranes (58% vs 30%, OR 3.18, 95% CI 1.33‑7.83), but not overall (44% vs 30%, OR 1.81, 95% CI 0.92‑3.54). Am J Obstet Gynecol 1999;180:1297‑302.

Abstract

<h2>Abstract</h2> <b>Objective:</b> The rarer allele of a polymorphism within the promoter region at position –308 of the gene for tumor necrosis factor α is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth. <b>Study Design:</b> We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered 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 premature rupture of the fetal membranes (n = 26). <b>Results:</b> Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position –308 in the gene for tumor necrosis factor α were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, <i>P</i> = .08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (<i>P</i> = .008, odds ratio 3.18, 95% confidence interval 1.33-7.83). <b>Conclusions:</b> Our results demonstrate an association between allelic variants of the polymorphism at position –308 in the gene for tumor necrosis factor α and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor α to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery. (Am J Obstet Gynecol 1999;180:1297-302.)