| Abstract: | When poisons enter the human body, tumor necrosis factor (TNF-alpha) will increase and cause damage to tissues through oxidative stress or inflammatory reaction. In previous studies, arsenic (As) has known to cause many health problems. Some studies have shown that As exposure is negatively correlated with estimated glomerular filtration rate (eGFR), or with the prevalence of proteinuria. At present, there are few studies focusing on the effects of As exposure and TNF-alpha single nucleotide polymorphism (SNP) to eGFR; thus, this study was intended to explore the interactions between TNF-alpha SNPs and plasma As and their effects on eGFR. A cohort of 500 adults, aged 30 to 70 years, was randomly selected from Taiwan Biobank (TWB). We used the gene chip to screen out seven SNPs of the TNF-alpha gene and used the results, combined with questionnaires, biochemical tests, and stored plasma samples from the TWB, for the analysis of As by inductively coupled plasma mass spectrometry (ICP-MS). After adjustments for BMI, hypertension, hyperlipidemia, kidney stones, and smoking habits, multiple regression statistics were performed to explore the interaction between SNPs and plasma As with eGFR. In this sample of the general population, plasma As had a significant association with the decline of eGFR (beta (SE) = -7.92 (1.70), p < 0.0001). TNF-alpha gene SNP rs1800629 had the property of regulating TNF-alpha, which interacts with plasma As; individuals with the AG type had a significantly lower eGFR than those with the GG type, by 9.59 mL/min/1.73 m(2) (p < 0.05), which, regarding the dominant model, could infer that the A allele is a risk allele. SNP rs769177 had no interaction with plasma As; however, participants with the TT or TC type had significantly higher eGFR levels than the CC carriers, by 4.02 mL/min/1.73 m(2) (p < 0.05). While rs769176 interacted with plasma As, if a person with the TC type had a higher plasma As concentration, that would sustain higher eGFR. This study found that certain SNPs of the TNF-alpha gene would be robust to the decline of eGFR caused by As exposure. Still, we need further research to confirm the protective regulation mechanism of these SNPs. |
