Relationship of blood aryl hydrocarbon receptor mRNA and cytochrome P450 1A1 mRNA expression with corrected QT interval among residents exposed to arsenic via drinking water

Abstract

To investigate the relationship between blood aryl hydrocarbon receptor(AhR)mRNA and cytochrome P450(CYP)1A1 mRNA expression and corrected QT interval among residents exposed to arsenic via drinking water. Arsenic exposure area in Bayannao'er city of Nei Monggol Autonomous Region was selected as the survey point, and the residents living more than 10 years in this area were investigated from December 2012 to January 2015.A total of 233 residents were divided into four groups according to drinking water arsenic concentration (ranged from 0.8 to 824.7 μg/L): control group (drinking water arsenic concentration <10.0 μg/L, n=55), low exposure group (drinking water arsenic concentration 10.0-99.9 μg/L, n=47), middle exposure group (drinking water arsenic concentration 100.0-199.9 μg/L, n=45), high exposure group (drinking water arsenic concentration ≥200.0 μg/L, n=86). Epidemiological investigation was performed.Real-time PCR technology was used to detect the expression levels of blood AhR mRNA and CYP1A1 mRNA, and the relationship between expression levels of blood AhR mRNA and CYP1A1 mRNA and corrected QT interval was analyzed. (1) Blood AhR mRNA and CYP1A1 mRNA expression levels were similar among control group, low exposure group and middle exposure group (all P>0.05) while blood AhR mRNA (3.18×10(-3)(2.42×10(-3), 4.45×10(-3)) vs.2.30×10(-3)(1.53×10(-3), 3.20×10(-3)), P<0.05) and CYP1A1 mRNA (1.58×10(-3)(0.80×10(-3), 2.73×10(-3))vs.1.00×10(-3)(0.59×10(-3), 2.09×10(-3)), P<0.05) expression levels were significantly higher in high dose group than in control group.(2) AhR mRNA expression level was similar between residents with longer corrected QT interval and residents with normal corrected QT interval (2.89×10(-3)(1.90×10(-3), 3.71×10(-3)) vs.2.58×10(-3)(1.85×10(-3), 3.57×10(-3)), P>0.05). CYP1A1 mRNA expression level was significantly higher in residents with longer corrected QT interval than in residents with normal corrected QT interval (1.50×10(-3)(0.78×10(-3), 2.63×10(-3)) vs.1.16×10(-3)(0.64×10(-3), 2.36×10(-3)), P<0.05). (3) AhR mRNA expression level was similar between residents with sinus tachycardia or bradycardia or normal heart rate(2.89×10(-3)(1.71×10(-3), 4.45×10(-3)) vs.2.64×10(-3)(1.86×10(-3), 3.52×10(-3)), P>0.05). CYP1A1 mRNA expression level was significantly higher in residents with sinus tachycardia or bradycardia than in residents with normal heart rate (1.47×10(-3)(0.87×10(-3), 2.77×10(-3)) vs.1.24×10(-3)(0.64×10(-3), 2.31×10(-3)), P<0.05). Long-term exposure to arsenic is associated with upregulated blood AhRmRNA and CYP1A1 mRNA expression.Blood CYP1A1 mRNA expression, but not AhRmRNA expression, is associated with prolonged corrected QT interval.