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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-01292008-133131 |
| Date | 05 February 2008 |
| Creators | Velez, Digna Rosa |
| Contributors | Jonathan Haines, Jeffrey Canter, John Jeffery Reese, Scott M. Williams, Marylyn D. Ritchie |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu//available/etd-01292008-133131/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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