Mendelian study on air pollution and membranous nephropathy outcomes associations
Xiaoxiao Zhu1, Hanjing Zhou2, Wanxian Xu3,4
1Traditional Chinese Medicine (Zhong Jing) College, Henan University of Chinese Medicine, Zhengzhou, China.
Abstract:
Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus, which mainly leads to nephrotic syndrome. This study investigates the associations between air pollution and MN risk and from an epigenomic perspective. In this study, we examine the associations between genetically predicted deoxyribonucleic acid methylation related to air pollution and MN risk. The data of air pollution included particulate matter (PM) with a diameter of 2.5 µm or less (PM2.5), PM with a diameter between 2.5 and 10 µm (PM2.5-10), PM with a diameter of 10 µm or less (PM10), nitrogen dioxide, and nitrogen oxides. Inverse variance weighted method was used as the main analysis method, and weighted median model and Mendelian randomization-Egger methods were selected for quality control. To assess the reliability of the results of the analyses, heterogeneity test, horizontal pleiotropy test, and the leave-one-out method were applied. There was a causal relationship between nitrogen oxides and MN risk (P = .010). Other types of air pollution were found no statistical association with MN disease (PM2.5: P = .378; PM2.5-10: P = .111; PM10: P = .035; nitrogen dioxide: P = .094). There was no heterogeneity or pleiotropy in the results. Our study suggests the association between nitrogen oxides and membrane nephropathy (MN) risk from the genetic perspective. This provides a theoretical basis for the prevention of MN disease.
Insights
This study found a causal link between nitrogen oxides in air pollution and an increased risk of membranous nephropathy (MN), an autoimmune kidney disease. Findings suggest a genetic basis for this association, aiding in MN disease prevention strategies.
Area of Science:
- Environmental Epigenetics
- Nephrology
- Toxicology
Background:
- Membranous nephropathy (MN) is an autoimmune glomerular kidney disease causing nephrotic syndrome.
- Air pollution is a growing environmental concern with potential health impacts.
- Epigenomic factors, like DNA methylation, may mediate environmental exposures and disease risk.
Purpose of the Study:
- To investigate the association between genetically predicted DNA methylation related to air pollution and the risk of membranous nephropathy (MN).
- To explore potential causal relationships between various air pollutants and MN risk from an epigenomic perspective.
Main Methods:
- Utilized Mendelian randomization (MR) analysis, including inverse variance weighted (IVW), weighted median, and MR-Egger methods.
- Assessed air pollutants: PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides.
- Employed heterogeneity, pleiotropy, and leave-one-out tests to ensure result reliability.
Main Results:
- A statistically significant causal relationship was identified between nitrogen oxides exposure and increased MN risk (P = .010).
- No significant associations were found between PM2.5, PM2.5-10, PM10, or nitrogen dioxide and MN risk.
- The study confirmed no significant heterogeneity or pleiotropy in the observed associations.
Conclusions:
- Nitrogen oxides exposure is associated with an increased risk of membranous nephropathy (MN) through a genetically predicted epigenomic pathway.
- This research provides a theoretical foundation for understanding the environmental determinants of MN and developing preventative measures.
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