Understanding epistatic interactions between transgenes and native genes is critical for predicting the response of transgenes to different genetic backgrounds and environments. Our objective was to determine if predicted epistatic interactions occur between maize (Zea mays L.) transgenes carrying zein promoters and opaque2, a transcriptional regulator of zein genes. Expression of the transgenes was significantly decreased in kernels containing the opaque2 mutation. Native zein proteins in these kernels were reduced as well. Thus, transgene expression mirrored expression of the native gene that contributed the promoter of the transgene. This work demonstrates that information about native gene expression may be useful for predicting transgene expression, reducing the risk of unintended consequences of transgene expression.