Associations of diet and lifestyle factors with oxidative stress and inflammation biomarkers according to antioxidant enzyme and DNA repair genetic risk scores Pubblico

Abstract

Oxidative stress and inflammation are involved in the etiology of several chronic diseases. Numerous diet and lifestyle factors are associated with oxidative stress and inflammation; however, little is known about associations of genetic factors, individually or jointly with environmental factors, and their associations with systemic oxidative stress and inflammation. We investigated associations of environmental and genetic exposures, separately and jointly, with circulating biomarkers of oxidative stress (F2-isoprostanes [FiP]) and inflammation (high sensitivity C-reactive protein [hsCRP]) in two pooled cross-sectional studies (n=465). We collected blood samples and extensive medical, dietary, and lifestyle data. Fifteen pro- and anti-oxidant dietary and lifestyle exposures were selected a priori for an oxidative balance score (OBS), with higher scores representing greater antioxidant exposures. Twenty-two single nucleotide polymorphisms (SNPs) in three antioxidant enzyme (AE) genes, and 79 SNPs in 14 DNA base excision repair (BER) genes were genotyped and used to develop AE and BER genetic risk scores (GRS). Multivariable general linear regression was used to assess adjusted mean FiP and hsCRP concentrations across tertiles of the OBS and GRS, separately and jointly. The mean FiP and hsCRP concentrations among those in the highest relative to the lowest tertiles of the OBS were, proportionately, 19.04% (p<0.0001) and 27.76% (p=0.02) lower, respectively. The corresponding findings for the AE GRS were 7.45% (p=0.02) and 35.54% (p=0.01) higher, and for the BER GRS they were 14.51% (p=0.04) and 48.92% (p=0.01) higher concentrations. Relative to those in the joint low OBS/high GER group (the hypothesized highest risk group), participants in the high OBS/low AE or BER GRS groups (the hypothesized lowest risk groups) had lower mean hsCRP concentrations compared to participants in the high risk tertile of either the OBS or the GRS, a pattern not found for FiP concentrations. Our findings suggest that environmental factors and antioxidant enzyme and DNA base excision repair genotypes may affect systemic inflammation and oxidative stress, and that they may synergize in affecting systemic inflammation, but not oxidative stress.

Table of Contents

Title/Abstract (1)

Introduction (2)

Methods (5)

Study design and population (5)

Data collection (6)

Data analysis (7)

    Exclusions (7)

    Oxidative Balance Score (OBS) (8)

    Genetic Risk Scores (GRS) (8)

    Analyzing associations of the OBS and GRS with FiP and hsCRP (9)

Results (10)

Discussion (12)

References (18)

Tables (24)

Appendices (29)

About this Master's Thesis

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School	Rollins School of Public Health
Department	Executive Masters of Public Health - MPH
Subfield / Discipline	Applied Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Parola chiave	antioxidant enzyme genetic risk score inflammation oxidative stress single nucleotide polymorphism biological marker DNA base excision repair oxidative balance score
Committee Chair / Thesis Advisor	Bostick, Roberd M., Emory University

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