Effects of prenatal tobacco exposure on gene expression profiling in umbilical cord tissue.

Maternal smoking doubles the risk of delivering a low birth weight infant. The purpose of this study was to analyze differential gene expression in umbilical cord tissue as a function of maternal smoking, with an emphasis on growth-related genes. We recruited 15 pregnant smokers and 15 women who never smoked during pregnancy to participate. RNA was isolated from umbilical cord tissue collected and snap frozen at the time of delivery. Microarray analysis was performed using the Affymetrix GeneChip Scanner 3000. Six hundred seventy-eight probes corresponding to 545 genes were differentially expressed (i.e. had an intensity ratio > +/- 1.3 and a corrected significance value p < 0.005) in tissue obtained from smokers versus nonsmokers. Genes important for fetal growth, angiogenesis, or development of connective tissue matrix were upregulated among smokers. The most highly upregulated gene was CSH1, a somatomammotropin gene. Two other somatomammotropin genes (CSH2 and CSH-L1) were also upregulated. The most highly downregulated gene was APOBEC3A; other downregulated genes included those that may be important in immune and barrier protection. Validation of the three somatomammotropin genes showed a high correlation between qPCR and microarray expression. We conclude that maternal smoking may be associated with altered gene expression in the offspring.