TITLE:
Association of Global DNA Hypermethylation with Hypertension, 8-oxo-7,8-dihydro-2’-deoxyguanosine, and Uracil Misincorporation: A Cross-Sectional Study on Taxi-Motorbike Drivers Working in Cotonou, Benin
AUTHORS:
Patrice Hodonou Avogbe, Elise Jeannesson-Thivisol, Christelle Yelognisse Ahomadegbe, Arnaud Zinsou Vinouyon Henry, Megnisse Catherine Gwladys Monligui, Stella Gloria Quist, Gbèna Ulrich Evrard Lokonon, Thimoléon Kizito Agbessy, Mauril Houtchai, Achille Martial Nouchet, Sodjiné Déo-Gracias Hountokoude, Iré Carine Olodo, Ambaliou Sanni
KEYWORDS:
5-methyl-2’-deoxycytidine, 8-oxo-2’-deoxyguanosine, Methylmalonic Acid, Oxidative Stress, Taxi-Motorbike Drivers, Uracil Misincorporation
JOURNAL NAME:
Open Journal of Genetics,
Vol.15 No.4,
December
22,
2025
ABSTRACT: Background: Occupational exposures are known contributors to oxidative stress and epigenetic alterations, but their interrelationships in highly exposed, vulnerable populations remain poorly characterized. This study investigates the associations between oxidative DNA damage, one-carbon metabolism biomarkers, and global DNA methylation in taxi-motorbike drivers (TMDs) in Cotonou, Benin—an occupational group with high exposure to traffic-related air pollution and a documented high prevalence of cardiometabolic risk factors. Methods: In this cross-sectional study, 138 male, non-smoking TMDs (mean age 39.4 ± 7.8 years; median occupational exposure 10 years) were included. We assessed cardiometabolic parameters, nutritional biomarkers [folate, vitamin B12, homocysteine, methylmalonic acid (MMA)], and, using a validated UPLC-MS/MS method, quantified oxidative DNA damage markers [uracil misincorporation (dU) and 8-oxo-2’-deoxyguanosine (8-oxodG)] and global DNA methylation (5-methyl-2’-deoxycytidine, 5mdC) from white blood cell DNA. Participants were stratified into tertiles based on %5mdC levels. Multivariable logistic regression was used to identify independent predictors of global DNA hypermethylation. Results: Markers of oxidative DNA damage were elevated, with median dU at 13.1 nmol/L and 8-oxodG at 5.7 nmol/L. The average level of 5mdC was 5.4%. Participants in the highest %5mdC tertile (>5.6%) had significantly higher systolic (140.0 mmHg, p = 0.010) and diastolic blood pressure (88.8 mmHg, p = 0.012) and a greater 10-year Framingham cardiovascular risk (8.7%, p = 0.013) compared to the lowest tertile. They also exhibited markedly elevated levels of dU and 8-oxodG (p = 0.020 and p = 0.004, respectively). After adjustment for confounders, logistic regression models identified 8-oxodG (aOR = 1.23, 95% CI: 1.04 - 1.45, p = 0.016) and dU (aOR = 1.07, 95% CI: 1.01 - 1.13, p = 0.014) as significant independent predictors of global DNA hypermethylation. Interestingly, MMA was inversely associated with DNA methylation levels (aOR = 0.99, 95% CI: 0.98 - 0.99, p = 0.008). Conclusion: Global DNA hypermethylation is significantly associated with increased oxidative DNA damage and adverse cardiometabolic outcomes in TMDs cohort. Our findings suggest oxidative stress as a key driver of epigenetic alterations while highlighting a potential protective role for adequate functional vitamin B12 status. This underscores a crucial interaction between oxidative stress, one-carbon metabolism, and epigenetics. Further longitudinal studies are needed to clarify the temporal sequence of these relationships and to explore interventions targeting oxidative stress or nutritional factors as strategies to mitigate epigenetic risk in high-exposure occupational groups.