{"doi":"10.3389/fragi.2023.1000166","title":"Antioxidant enzyme and DNA base repair genetic risk scores’ associations with systemic oxidative stress biomarker in pooled cross-sectional studies","abstract":"Background: 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. Methods: 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 ( n = 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 2 -isoprostanes (FiP) concentrations, we selected 4 GSTP1 SNPs for an AE GRS, and 12 SNPs of 5 genes ( XRCC1 , TDG , PNKP , MUTYH , and FEN1 ) 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. Results: 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% ( p = 0.12) and 21.2% ( p = 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. Conclusion: 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.","journal":"Frontiers in Aging","year":2023,"id":406631,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9273,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":978736,"name":"Abigail L. H. Gray","orcid":null,"position":1,"is_corresponding":false},{"id":303810,"name":"Bharat Thyagarajan","orcid":"0000-0001-6968-6985","position":2,"is_corresponding":false},{"id":339565,"name":"Roberd M. Bostick","orcid":"0000-0001-8626-4186","position":3,"is_corresponding":false},{"id":978360,"name":"Ziling Mao","orcid":"0000-0001-9601-2468","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:03.432924Z","pmid":"37152862","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}