| Title: | From genes to clinic: Genomic and cross-sectional cohort analysis of oxidative stressors and lipid metabolism in European ancestry |
| Journal: | Cytokine |
| Published: | 20 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40252476/ |
| DOI: | https://doi.org/10.1016/j.cyto.2025.156941 |
Publication 15474
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Abstract
BACKGROUND: The link between oxidative stress and lipid metabolism is widely studied, but their causal relationship in the general population remains unclear.</p>
METHODS: We utilized weighted regression and propensity score matching (PSM) models to investigate the relationship between endogenous oxidative stress markers (serum bilirubin and uric acid) and lipid metabolism in 11,087 participants of European ancestry from the National Health and Nutrition Examination Survey (NHANES) during the period from 2005 to 2018. Additionally, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) summary statistics from individuals of European ancestry (n = 997 to 575,531) to explore the genetic causal relationship between oxidative stress markers and lipid metabolism profiles (n = 20,430).</p>
RESULTS: Weighted regression showed that serum uric acid significantly increased high cholesterol (OR = 1.11, 95 % CI = 1.06-1.15, P < 0.001) and high triglycerides (OR = 1.25, 95 % CI = 1.20-1.30, P < 0.001). PSM analysis confirmed that serum uric acid increased the incidence of high triglycerides (OR = 1.57, 95 % CI = 1.35-1.82, P < 0.001). Additionally, a strong bidirectional genetic relationship was found between oxidative stress markers and lipid metabolism. For example, serum uric acid increased serum triglycerides (β = 0.1904, Se = 0.05, P < 0.001) and decreased total cholesterol in very large HDL (β = -0.1298, Se = 0.039, P < 0.001). Conversely, total cholesterol reduced direct bilirubin levels (β = -0.1707, Se = 0.018, P < 0.001). No significant horizontal pleiotropy was detected by MR-Egger intercept.</p>
CONCLUSION: Our findings demonstrate a robust genetic and population-based association between oxidative stress markers and lipid metabolism, suggesting potential therapeutic targets for lipid disorders based on endogenous oxidative stressors.</p>
19 Keywords
- Adult
- Bilirubin
- Biomarkers
- Cohort Studies
- Cross-Sectional Studies
- Female
- Genome-Wide Association Study
- Genomics
- Humans
- Lipid Metabolism
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Oxidative Stress
- Polymorphism, Single Nucleotide
- Triglycerides
- United States
- Uric Acid
- White
3 Authors
- Bo He
- Yingjie Li
- Ning Zhou
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