AUTHOR=Tao Na , Li Lianhong , Chen Qing , Sun Zhongming , Yang Qinglin , Cao Dafang , Zhao Xun , Zeng Fangfang , Liu Jun TITLE=Association Between Antioxidant Nutrients, Oxidative Stress-Related Gene Polymorphism and Skeletal Fluorosis in Guizhou, China JOURNAL=Frontiers in Public Health VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.849173 DOI=10.3389/fpubh.2022.849173 ISSN=2296-2565 ABSTRACT=Background: Oxidative stress plays an important role in the pathogenesis of endemic fluorosis. We analyzed associations between oxidative stress-related gene polymorphisms (PON1 rs662, CAT rs769217, rs2300182, SOD2 rs11968525) and skeletal fluorosis, and examined potential gene–environment interactions with dietary vitamin C, vitamin E, zinc, and selenium intake. Methods: A cross-sectional study was conducted in Zhijin County, Guizhou province of China. Skeletal fluorosis was identified according to the Chinese Diagnostic Criteria of Endemic Skeletal Fluorosis. Dietary information was assessed through face-to-face interviews by trained interviewers using a 75-item food frequency questionnaire. The genotype was detected by high throughput TaqMan-MGB RT-PCR technology. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using an unconditional logistic regression model. Results: Intake of vitamin E, zinc and selenium was found to be inversely associated with the risk of skeletal fluorosis. The multivariable adjusted ORs were 0.438 (95% CI : 0.268 to 0.715, P-trend < 0.001) for Vitamin E , 0.490 (95% CI: 0.298 to 0.805, P-trend = 0.001) for zinc and 0.532 (95% CI: 0.324 to 0.873, P-trend = 0.010) for selenium when comparing the highest with the lowest quartile. The relationship for vitamin C was not observed after adjustment for risk factors. Furthermore, participants with PON1 rs662 AA genotype had a significantly decreased risk of the skeletal fluorosis compared to those with the GG genotype (OR = 0.438, 95% CI: 0.231 to 0.830). GG+AG genotype carriers were 2.212 times more likely to have skeletal fluorosis than AA carriers (OR = 2.212, 95% CI: 1.197 to 4.090). Compared to AA carriers, AG carriers had a 2.182 times higher risk of skeletal fluorosis (OR = 2.182, 95% CI: 1.143 to 4.163). Although, we observed the risk of skeletal fluorosis was higher with lower intake of antioxidant nutrients, the potential interactions between nutrient intake and genetic polymorphisms were not observed. Conclusions: Participants with a higher intake of vitamin E, zinc and selenium have a lower likelihood of skeletal fluorosis. Additionally, the PON1 rs662 polymorphism is related to skeletal fluorosis.