Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study.
BACKGROUND
Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.


METHODS
As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip(R) Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.


RESULTS
A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.


CONCLUSIONS
PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.
Enquobahrie
Daniel A
DA
Department of Epidemiology, University of Washington, Seattle, WA, USA. danenq@u.washington.edu
Williams
Michelle A
MA
Qiu
Chunfang
C
Muhie
Seid Y
SY
Slentz-Kesler
Kimberly
K
Ge
Zhaoping
Z
Sorenson
Tanya
T
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D012313:RNA / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D012333:RNA, Messenger; D012313:RNA