Effect of phenol exposure and single nucleotide polymorphisms interaction on renal function
Objective To investigate of the interaction between exposure to bisphenol A(BPA),bisphenol F(BPF),triclosan(TCS)and gene locus polymorphism on renal function.Methods A total of 414 adults were recruited as research subjects from the physical examination population of Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology between 2016 and 2021.Population information was collected through questionnaires,and urine samples were obtained for analysis.The internal exposure levels of three phenolic compounds,namely BPA,BPF,and TCS,were subsequently measured in the urine samples of the study subjects.Serum creatinine levels were measured to determine renal function,and eGFR was calculated as an indicator.Blood samples were taken from research subjects to extract DNA for high-throughput genotyping,genome filling,and quality control.Genome-wide association studies(GWAS)were then conducted to analyze gene-environment interactions affecting eGFR levels.Finally,the obtained significant and suggestive genetic loci were annotated by location and function to explore their related biological functions.Results Following high-throughput genotyping and genotype filling,414 samples were obtained with genotype data for 4 135 024 single nucleotide polymorphisms(SNPs)loci.During further identification,three SNPs loci(rs60391380,rs56108314,and rs73082740)were found to have a significant interaction with BPA in relation to renal function.These loci were located in the 4pl6.3 chromosome segment,close to the ADRA2C gene.The most significant interaction effect was found for rs60391380,with a beta value of-0.042(-0.057--0.028)and a P-value of 1.565×10-8.Based on epigenetic modifications,it was speculated that this genetic locus might interact with BPA,activate its regulatory elements,and upregulate the expression of ADRA2C,thereby affecting renal function.Additionally,844 BPA interaction sites were explored,with suggestive results(P＜5× 10-6).In the eGFR genome-wide associa-tion analysis,52 loci were found to interact with BPF in a suggestive manner,but no significant loci were identified.For TCS,no significant or suggestive sites of interaction were found.Conclusions The interaction between BPA and SNPs had a joint effect on renal function.However,no statistically significant gene-environment interactions affecting renal function were found for BPF and TCS.
万方数据
维普
