A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth.

The rarer of 2 alleles of a polymorphism in the promoter of the tumor necrosis factor alpha gene (TNF) has been associated with spontaneous preterm birth following preterm premature rupture of the fetal membranes in some populations. The aim of this study was to assess if the presence of symptomatic bacterial vaginosis amplifies the risk of spontaneous preterm birth in those with a "susceptible" TNF genotype. A case-control study was performed at our institution. Cases (n=125) were defined as women who delivered before 37 weeks as a result of ruptured membranes or preterm labor, while control subjects (n=250) were defined as women who delivered after 37 weeks. DNA was collected from maternal blood and analyzed for the TNF genotype. Information on symptomatic bacterial vaginosis and other risk factors for preterm birth was obtained by review of the antenatal record. Multiple logistic regression was also used to test the interaction between bacterial vaginosis, the TNF genotype, and preterm birth. Maternal carriers of the rarer allele (TNF-2) were at a significantly increased risk of spontaneous preterm birth [odds ratio (OR) 2.7, 95% CI 1.7-4.5]. The association between TNF-2 and preterm birth was modified by the presence of bacterial vaginosis, such that those with a "susceptible" genotype and bacterial vaginosis had increased odds of preterm birth compared with those who did not (OR 6.1, 95% CI 1.9-21.0). This study provides preliminary evidence that an interaction between genetic susceptibilities (ie, TNF-2 carriers) and environmental factors (ie, bacterial vaginosis) is associated with an increased risk of spontaneous preterm birth.