29: Maternal and fetal genetic associations with preterm delivery


      To determine genetic risk factors for PTD within 159 selected candidate genes in different PTD pathways.

      Study Design

      The study consisted of 430 maternal DNA samples (213 cases, 217 controls) and 425 fetal DNA samples (209 cases, 216 controls) nested within the Norwegian Mother Child Cohort study. We studied 1453 markers from the 159 genes selected.


      For maternal samples the most significant association was a marker (rs2472) in the collagen, type 1, alpha-2 (COL1A2) gene (allelic p-value=1.14x10-3, genotypic p-value=1.09x10-3). The odds ratio (OR) for this SNP was 0.31 (95% CI 0.15-0.64, p-value=0.001) for a recessive model. Haplotype analysis of this gene revealed multiple significant haplotypes, the strongest being a 3 marker haplotype (p=0.003). This gene is involved in the extracellular matrix (ECM) receptor interaction pathway; additionally there were significant associations in 3/4 other genes involved in this pathway. Perturbations in this pathway may lead to ECM degradation, myometrial activation and eventually PTD. In fetal samples the most significant association in fetal samples was a marker (rs6434222) in the tissue factor pathway inhibitor (TFPI) gene (allelic p-value=7.88x10-5, genotypic p-value=1.40x10-4). The OR for this SNP was 2.56 (95%CI=1.60-4.10, p-value<0.001) for a recessive model. Haplotype analysis of this gene revealed several significant associations, the most significant being a 4 marker haplotype (p-value 2.6x10-4). This marker is part of the complement and coagulation pathway which is important in decidual hemorrhage, a primary pathway of PTD. Additionally, there were 4/12 other genes in this pathway with significant associations.


      This study identified several genes associated with PTD and maternal and fetal pathway breakpoints contributing to PTD.