Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in its infancy.

Purpose: The purpose of conducting this cross-sectional research study was to identify both positive and negative associations between lifestyle factors (e.g., diet, exercise, smoking habits, and stress) and high-sensitivity C-reactive protein (hs-CRP) in healthy people with differing IL-1 gene polymorphisms. It was expected that people who have a genotype associated with over-expression of IL-1 would have higher serum levels of hs-CRP. It was also expected that IL-1 genotype would modify the association between hs-CRP and selected lifestyle factors.

Methodology: We evaluated 2,328 healthy adults from eight study sites across the United States from September 2003 - April 2005. Serum hs-CRP was measured as a non-specific marker for systemic inflammation. DNA extracted from a whole blood sample was used to determine single nucleotide polymorphisms in the IL-1 gene. General health and lifestyle information was collected on the 38-question Personal Wellness Profile Concise Assessment Plus questionnaire. The relationship between CRP, IL-1 genotype, and lifestyle factors was evaluated using linear and logistic regression models adjusted for covariates.

Results: No association was found between IL-1 genotype and CRP level. The strongest predictor of CRP was body mass index (BMI) and to a lesser extent age, Hispanic ethnicity, diastolic blood pressure (DBP), alcohol consumption, and type of carbohydrate consumed. The ability of BMI to predict CRP was strengthened in females with a genotype associated with over-expression of IL-1.

Conclusion: While IL-1 genotype was not predictive of CRP levels in this healthy population, it did affect the relationship between BMI and CRP in females.

Significance to Preventive Care: Our study supports the existing body of research showing a strong relationship between BMI and CRP. Lifestyle modifications that support a healthy BMI will positively affect CRP as well as the other established risk factors for CVD. Understanding IL-1 gene polymorphisms is important for understanding the mechanisms of action involved in inflammation-directed therapies. However, until more is understood regarding the relationship of IL-1 polymorphisms to CRP reduction and reduced disease risk, it is not appropriate at this time to make public health recommendations based upon the IL-1 genotype.

School

School of Public Health

First Advisor

Edward K. Fujimoto

Second Advisor

W. Lawrence Beeson

Third Advisor

Lee Berk

Degree Name

Doctor of Public Health (DrPH)

Degree Level

Ph.D.

Year Degree Awarded

2007

Date (Title Page)

3-2007

Language

English

Library of Congress/MESH Subject Headings

Cardiovascular Diseases -- prevention and control; Life Style; Health Behavior; C-Reactive Protein; Polymorphism, Genetic

Type

Dissertation

Page Count

ix; 116

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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