Interplay of cytokine polymorphisms and bacterial vaginosis in the etiology of preterm delivery

Recent findings suggest that the association between inflammation-related genes and preterm delivery may be stronger in the presence of bacterial vaginosis (BV). Tumor necrosis factor-alpha (TNFα) and interleukin 1-beta (IL-1β) are pro-inflammatory cytokines capable of inducing preterm labor in non-human primates. In this study the authors tested associations among two TNFα promoter polymorphisms (−G308A and −G238A), a single IL-1β polymorphism (+C3954T), vaginal microbial findings, and risk of preterm delivery. Data were from the Pregnancy Outcomes and Community Health (POUCH) Study (n = 777 term and n = 230 preterm deliveries). Vaginal smears collected at mid-pregnancy (15-27 weeks gestation) were scored according to Nugent's criteria. A Nugent score of ≥4 was modeled as the cut-point for intermediate and positive BV. Logistic regression was used to estimate odds ratios for associations among independent covariates (vaginal flora, genotype) and preterm delivery. Results showed that women with a Nugent score of ≥ 4 and the TNFα −238 A/G or A/A were at increased risk of delivering preterm (race/ethnicity adjusted OR 2.6, 95% CI 1.2, 5.8). The p-value for the genotype and Nugent score interaction = 0.02. This study points to one more example of a potential gene-environment interaction in a preterm delivery pathway. Future tests of this finding will determine the robustness of these results.