Interactive Effects Between Lead-Cadmium Co-exposure and VEGFA Gene Polymorphisms on Renal Dysfunction: A Gene-Environment Interaction Study

Yaotang Deng^1,2Yunman Wen²Weixia Duan¹Zhiqiang Zhao²Guoliang Li²Jiazhen Zhou²Le Yang²Jieyi Yang²Yapei Sun¹Manyi Qiu²Lili Liu^2*

• ¹Chongqing Key Laboratory of Prevention and Treatment for Occupational Diseases and Poisoning, The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College, Chongqing, China
• ²Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China

Background: Lead (Pb) and cadmium (Cd) are common persistent environmental pollutants, may cause renal dysfunction following long-term exposure. This study investigated whether Vascular Endothelial Growth Factor A (VEGFA) gene polymorphisms modify the association between Pb and Cd exposure with renal dysfunction risk, given the key role of gene-environment interactions in kidney pathogenesis. Methods: A cross-sectional study of 408 workers was undertaken from a Pb-Cd smelter in Guangdong Province, China in 2023. Metals in blood and urine were measured using Inductively coupled plasma-Mass Spectrometry (ICP-MS). Additive, dominant and recessive genetic models were employed to analyze differences in genotype distribution of rs3025010, rs10434 and rs833061 between normal and renal dysfunction groups. Interaction analyses were conducted to examine the combined effects of blood lead (BPb) and urinary cadmium (UCd) exposure with these polymorphisms under different genetic models on renal dysfunction risk. Results: For rs833061 locus, BPb showed statistically significant differences in both the additive and recessive models (p<0.05), while renal function exhibited differences in the additive and dominant models (p<0.05). For rs3025010, BPb showed significant differences in the recessive model (p=0.05), and renal function demonstrated differences in both additive and dominant models (p<0.05). Multivariate regression analysis identified BPb and UCd as risk factors for renal dysfunction, with odds ratios ranging from 1.40 to 3.46 (p <0.05). Interaction analyses revealed interactions between rs3025010 and Pb [BPb×rs3025010: OR (95%CI) = 0.69(0.49, 0.88)] in dominant model. The rs10434 locus interactions with Pb and Cd in both the additive [OR (95%CI) = 0.60 (0.31, 0.91)] and recessive models [OR (95%CI) = 0.51 (0.27, 0.85)]. Conclusion: This study identified significant gene-environment interactions between VEGFA polymorphisms (rs3025010 and rs10434) and Pb-Cd co-exposure in renal dysfunction. These findings suggest that screening for these polymorphisms could identify high-risk populations for targeted prevention and control strategies.