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Title page for ETD etd-01292008-133131

Type of Document Dissertation
Author Velez, Digna Rosa
URN etd-01292008-133131
Title Investigations into the genetic susceptibility to preterm birth
Degree PhD
Department Human Genetics
Advisory Committee
Advisor Name Title
Marylyn D. Ritchie Committee Chair
Jeffrey Canter Committee Member
John Jeffery Reese Committee Member
Jonathan Haines Committee Member
Scott M. Williams Committee Member
  • genetic epidemiology
  • genetics
  • preterm birth
Date of Defense 2008-01-25
Availability unrestricted
Spontaneous preterm birth (PTB), gestational age less than 37 weeks, is a major public health problem worldwide. Almost 500,000 preterm births occur annually in the United States (U.S.), accounting for ~12% of deliveries. The outcomes associated with PTB include increased risk of infant morbidity and mortality.

In addition to the effects on the health of the child, there is a significant disparity in incidence and clinical correlates of PTB between ethnic groups in the U.S. PTB, for example, among African Americans is ~18% compared to ~12% in Caucasians. Also, African American women who experience PTB are also more likely to have future PTB and early PTB associated with infection (less than 32 weeks gestation) than Caucasian women. Both the disparity in PTB rates and clinical correlates between ethnic groups in the U.S. may be explained by genetic causes.

An important aspect of PTB that distinguishes it from other phenotypes is that both maternal and fetal genes can affect pregnancy outcome. Because of the complex relationship between mother and fetus, the numerous factors affecting pregnancy and substantial selection for term delivery to ensure survival, it is unlikely that any single factor will be sufficient to explain PTB.

To better understand the genetic contribution to PTB and the rate disparity between ethnic groups, we performed a comprehensive genetic analysis. A high-throughput candidate gene screen and an analysis of amniotic fluid (AF) cytokine protein levels were performed to identify PTB risk factors. We selected candidate genes based on genes showing positive results in previous studies and/or being involved in hypothesized pathophysiological pathways. We selected 130 genes and 1536 single nucleotide polymorphisms (SNPs) from the nuclear genome and three candidate genes from the mitochondrial genome. We also examined AF protein concentration of seven well-established biomarkers of PTB for association with PTB. Our study indicates that several common risk factors in the infection and inflammatory response pathways may explain a portion of the risk in both Caucasians and African Americans; however, different genes lead to increased risk in Caucasians and African Americans, with the maternal influence being greater in Caucasians than in African Americans.

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