Since increased oxidative stress may mediate the detrimental actions of the enhanced sympathetic nervous activity on the renal function and vice versa, we investigated the effect of the polymorphic Arg16Gly in the β2 adrenoceptor (ADRB2) gene, Trp64Arg in the ADRB3 gene and C242T in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox gene on the estimated glomerular filtration rate (eGFR) in Chinese. Initially recruited from the different outpatient service of our hospitals, 668 individuals were finally eligible with complete demographic information. Laboratory tests were performed and eGFR was derived from the MDRD equation for the Chinese. Plasma norepinephrine level and genotype were determined by the high performance liquid chromatography and TaqMan method, respectively. Only across the Arg16Gly polymorphism did the eGFR show significant difference: it was lower in the Gly16Gly variation which also had the highest plasma norepinephrine level. This polymorphism still remained a significant determinant of the eGFR after the multivariate analysis. Of importance, the multifactor dimensionality reduction method further detected a significant synergism between the polymorphic Arg16Gly and C242T in the eGFR reduction. These observations clarified the effects of the studied polymorphisms on the eGFR and exemplified gene‐gene interaction influencing renal function. This article is protected by copyright. All rights reserved.