Alterations of Gene Expression In Preterm Birth: A Screening Study

Abstract

Preterm birth is classified by a baby being born 37 weeks or earlier. However, if a baby is born 32 weeks or earlier, they are at a higher risk for death and disabilities. Preterm babies cause more than half of long-term morbidity (suffering from a disease or medical condition) and 75% of prenatal death. Using the Preterm Birth Transcriptomic Database, these genes were screened using a variety of ways. To narrow down these genes, we initially used P-value, then later used FC Value, Val. Fold Change, and Log Fold Change to narrow down the genes. Screening second trimester maternal blood and third trimester maternal blood for significantly regulated genes revealed 42 potential gene candidates. Of these 42 genes, 22 (52.3%) were significantly altered in the third trimester based on p-value less than 0.05.  In the end 12 genes were picked for further evaluation. We grouped the genes into 4 major categories: immune system related, metabolism related, clot related, and development related. In summary of the 12 genes screened, TLR4 is our top gene candidate for preterm birth prevention. TLR4 is a part of the TLR (toll-like receptor) family, which plays an important role in pathogen recognition and innate immune activation. This gene and its inhibitor, TAK-242 would serve as a potential causative gene in preclinical mice models and testing of this drug needs to be conducted in various preclinical platforms with the end target of a Phase 1/2 clinical trial.