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Title page for ETD etd-11022015-122608


Type of Document Dissertation
Author Giri, Ayush
Author's Email Address ayush.giris@gmail.com
URN etd-11022015-122608
Title Modifiable and non-modifiable risk factors for pelvic organ prolapse
Degree PhD
Department Epidemiology
Advisory Committee
Advisor Name Title
Todd L. Edwards Committee Chair
Bingshan Li Committee Member
Digna R. Velez Edwards Committee Member
Katherine E. Hartmann Committee Member
Melinda C. Aldrich Committee Member
Keywords
  • Epidemiology of POP
  • Admixture mapping
  • Gene-environment interactions
  • Obesity and pelvic organ prolapse
  • Pelvic organ prolapse (POP)
  • Women's Health
Date of Defense 2015-09-28
Availability unrestricted
Abstract

Pelvic organ prolapse (POP) is characterized by the descent of pelvic organs (uterus, bladder, and bowels) from their normal anatomical positions into the vaginal space due to defects in the pelvic floor support system. Obesity may influence POP but findings from studies are not always consistent. A systematic-review of the literature was undertaken here and a meta-analysis was conducted to evidence that being over-weight and obese increased odds of having POP, compared with women with normal-weight. Literature suggests POP is heritable, and is likely influenced by a host of predisposing and modifiable factors; however this notion of interaction has not been formally assessed. Considering childbirth is the strongest risk factor and obesity, the most-practicably modifiable risk factor for POP, analyses were undertaken to identify whether single nucleotide polymorphisms (SNPs) in/around 96 candidate genes modify the associations between parity and POP and body mass index (BMI) and POP in European American, African American and Hispanic women from the Women’s Health Initiative Hormone Therapy (WHI-HT) trial. Although signals were not statistically significant considering multiple-comparisons, SNPs from several potential gene regions were noted to interact with BMI (COL11A1, CADM2, ELN, ACTN3, NRXN3, FTO, and TMEM160) and with parity (CADM2, ETV5, and ITPR2) to influence POP. Epidemiologic evidence also suggests racial disparity in POP prevalence; however, whether continental genetic ancestry plays a part has not been examined. An admixture mapping study of POP was undertaken in African American women from the WHI-HT. One chromosomal region (15:q262) showed a statistically significant inverse association with European ancestry, while another (1:q42.1-42.3) showed a suggestive positive association with European ancestry in relation to POP. This work demonstrates the multifactorial etiology of POP and the need to further investigate the mechanisms of how these factors interrelate to manifest POP.

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