Predicting risk of bacterial vaginosis: the role of race, smoking and corticotropin-releasing hormone-related genes

Bacterial vaginosis (BV) is one of the most prevalent vaginal disorders in adult women and is associated with adverse pregnancy outcomes such as pre-term birth. Genetic factors, particularly in genes involved in inflammation and infection, are associated with this condition. Additionally, environmental risk factors including stress and smoking are associated with BV. The purpose of this study was to identify genetic variants in stress-related genes such as corticotropin-releasing hormone (CRH), receptor 1, receptor 2 and binding protein (CRH-BP) that associate with BV. Also gene-environment effects with smoking are determined. BV was quantified using the Nugent score in 82 white and 65 black women in the first trimester of pregnancy. Associations between Nugent score, genotype and smoking were analyzed using Kruskal-Wallis and Wilcoxon rank sum non-parametric tests. In white women, non-smokers with the CT genotype at CRH-BP + 17487 have lower Nugent scores (median: 0, range: 0-0) than non-smokers with the TT genotype (median: 2, range: 0-8) (P = 0.002); whereas smokers with the CT genotype have higher Nugent scores (median: 6, range: 0-10) than smokers with the TT genotype (median: 1, range: 0-10) (P = 0.021). In black women, the AG genotype at CRH + 3362 or CRH - 1667 is associated with lower Nugent scores (median for both: 3, range: 0-10) compared with the homozygous genotypes (median for each homozygous genotype: 8, range: 0-10). Also, in black women, models remain significant after adjusting for smoking (P = 0.04 for both). These data indicate that susceptibility to BV is affected by patterns of genetic variation in stress-related genes and smoking plays an important role.