AUTHOR=Mao Ziling , Gray Abigail L. H. , Thyagarajan Bharat , Bostick Roberd M. 

TITLE=Antioxidant enzyme and DNA base repair genetic risk scores’ associations with systemic oxidative stress biomarker in pooled cross-sectional studies

JOURNAL=Frontiers in Aging

VOLUME=4

YEAR=2023

URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2023.1000166

DOI=10.3389/fragi.2023.1000166

ISSN=2673-6217

ABSTRACT=<p><bold>Background:</bold> Oxidative stress is hypothesized to contribute to the pathogenesis of several chronic diseases. Numerous dietary and lifestyle factors are associated with oxidative stress; however, little is known about associations of genetic factors, individually or jointly with dietary and lifestyle factors, with oxidative stress in humans.</p><p><bold>Methods:</bold> We genotyped 22 haplotype-tagging single nucleotide polymorphisms (SNPs) in 3 antioxidant enzyme (AE) genes and 79 SNPs in 14 DNA base excision repair (BER) genes to develop oxidative stress-specific AE and BER genetic risk scores (GRS) in two pooled cross-sectional studies (<italic>n</italic> = 245) of 30–74-year-old, White, cancer- and inflammatory bowel disease-free adults. Of the genotypes, based on their associations with a systemic oxidative stress biomarker, plasma F<sub>2</sub>-isoprostanes (FiP) concentrations, we selected 4 <italic>GSTP1</italic> SNPs for an AE GRS, and 12 SNPs of 5 genes (<italic>XRCC1</italic>, <italic>TDG</italic>, <italic>PNKP</italic>, <italic>MUTYH</italic>, and <italic>FEN1</italic>) for a BER GRS. We also calculated a previously-reported, validated, questionnaire-based, oxidative stress biomarker-weighted oxidative balance score (OBS) comprising 17 anti- and pro-oxidant dietary and lifestyle exposures, with higher scores representing a higher predominance of antioxidant exposures. We used general linear regression to assess adjusted mean FiP concentrations across GRS and OBS tertiles, separately and jointly.</p><p><bold>Results:</bold> The adjusted mean FiP concentrations among those in the highest relative to the lowest oxidative stress-specific AE and BER GRS tertiles were, proportionately, 11.8% (<italic>p</italic> = 0.12) and 21.2% (<italic>p</italic> = 0.002) higher, respectively. In the joint AE/BER GRS analysis, the highest estimated mean FiP concentration was among those with jointly high AE/BER GRS. Mean FiP concentrations across OBS tertiles were similar across AE and BER GRS strata.</p><p><bold>Conclusion:</bold> Our pilot study findings suggest that DNA BER, and possibly AE, genotypes collectively may be associated with systemic oxidative stress in humans, and support further research in larger, general populations.</p>