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Title page for ETD etd-01142009-105542


Type of Document Dissertation
Author Ryckman, Kelli Kae
URN etd-01142009-105542
Title The Genetics and Epidemiology of Reproductive Disorders
Degree PhD
Department Human Genetics
Advisory Committee
Advisor Name Title
Marshall L. Summar Committee Chair
Dana C. Crawford Committee Member
Hyagriv N. Simhan Committee Member
Jonathan L. Haines Committee Member
Scott M. Williams Committee Member
Keywords
  • bacterial vaginosis
  • pregnancy complications
  • preterm birth
  • Pregnancy -- Complications -- Epidemiology
  • Cytokines -- Physiological effect
  • Genetic disorders in pregnancy
  • Premature labor -- Etiology
Date of Defense 2008-12-10
Availability unrestricted
Abstract
Each year in the United States about one million (17%) of all pregnancies experience complications that result in fetal loss. Of the five million pregnancies that end in a live birth approximately 12% are born prematurely. Vaginal disorders and infections during pregnancy, particularly bacterial vaginosis (BV), are known risk factors for both miscarriage and preterm birth (PTB). Identifying the environmental and genetic risk factors for these complex reproductive disorders is important for improving health through better diagnostic methods and treatments.

The purpose of this project is to examine the genetics and epidemiology of BV and PTB as examples of complex reproductive disorders. Cervical immunity clearly plays an important role in the pathogenesis and progression of BV. Therefore, cervical cytokine concentrations were measured during the first trimester of pregnancy in BV positive (BV+) and BV negative (BV-) women. Genetic associations between cytokine receptor genes and cervical cytokine concentrations were identified and discovered to differ by both BV status and race.

The genetics of PTB was examined by genotyping approximately 1500 single nucleotide polymorphisms (SNPs) from 160 genes involved in preterm pathways, including decidual hemorrhage, infection and inflammation, activation of the hypothalamic-pituitary-adrenal axis, and uterine distention. SNPs in both the decidual hemorrhage and infection/inflammation pathways were associated with PTB. Additionally, many of these associations corroborate results from a previous association study.

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