Susceptibility to childhood asthma modified by the interactive effects of polycyclic aromatic hydrocarbons exposure and genetic polymorphisms of the aryl hydrocarbon receptor signaling pathway: functional analysis based on lipid metabolism.
Tao. Xuna X; Xu. Xinfeng X; Jiang. Xinyao X; Chen. Mingcong M; Bao. Yuling Y; Cao. Shuyuan S; Li. Lei L; Yang. Sheng S; Wu. Qian Q
Key Findings
- Higher blood levels of several PAHs were linked to increased childhood asthma risk.
- The CYP1A1 rs4646421‑AA genotype was associated with higher CYP1A1 expression and a 2.4‑fold higher odds of asthma.
- PAH exposure and the rs4646421 variant interact to further raise asthma risk, partly through changes in lipid metabolites and reduced C16‑ceramide production.
Practical Outcomes
- For biohackers and self‑directed health optimizers, this research provides no actionable protocols, dosage guidance, or direct benefits related to palmitoyl‑dipeptide‑6. It mainly adds mechanistic insight into childhood asthma risk factors, which is not immediately relevant to longevity, metabolic health, or performance optimization.
Summary
This study looked at how exposure to certain air pollutants (PAHs) and a specific gene variant (CYP1A1 rs4646421) together raise the risk of childhood asthma by messing with lipid metabolism in lung cells. It does not involve the peptide palmitoyl‑dipeptide‑6 and offers no direct advice for health‑optimizing practices.
Abstract
Exposure to polycyclic aromatic hydrocarbons (PAHs) is linked to the development of childhood asthma, but little is known about PAH exposure-single nucleotide polymorphisms (SNPs) involved in the aryl hydrocarbon receptor (AHR) signaling pathway interactions on childhood asthma. This study aimed to investigated the effects of PAH exposure interactions with SNPs in the AHR signaling pathway on childhood asthma and characterized the molecular pathway of asthma genetic risk based on the metabolome. A total of 370 children were included in the current study. Serum fluoranthene, benz(a)anthracene, chrysene, benzo(k)fluoranthene and benzo(a)pyrene levels were significantly associated with childhood asthma. SNP genotyping analysis revealed that CYP1A1 rs4646421 was significantly associated with childhood asthma (OR: 2.404, 95% CI: 1.542-3.747) in Chinese children. Generalized multifactor dimensionality reduction analysis showed significant interactions between PAH exposure and rs4646421, increasing the risk of childhood asthma. Expression quantitative trait loci analysis showed that the rs4646421-AA genotype was significantly associated with the increased expression of CYP1A1. Mediation analysis identified six serum lipid metabolites associated with rs4646421 that mediated the effect of the rs4646421-AA genotype on childhood asthma. To verify the potential biological function of rs4646421, a model of CYP1A1-overexpressing human bronchial epithelial cells was constructed. The results showed that CYP1A1 overexpression downregulated serine palmitoyl transferase expression by decreasing AHR/ARNT2 levels, and subsequently reduced C16-ceramide synthesis and upregulated the expression of inflammatory factors associated with asthma in the human bronchial epithelial cells. This study provided the evidence of the interactions between PAH exposure and CYP1A1 rs4646421 in increasing childhood asthma susceptibility in Chinese, suggesting that rs4646421 played a functional role in childhood asthma by affecting the expression of CYP1A1, thereby interfering with lipid metabolism.
Study Information
pubmed
2025
2025-11-28T00:00:00.000Z
10.1186/s12931-025-03428-x
36