Similarly, elderly subjects with a K- or J-variant of BChEmay require a careful introduction to duloxetine treatment, giventhat K and J mutations in the BCHE gene are often present togetherand result in a 30–60% intrinsic reduction in the BChE activity.6 There are also other phenomena that may arisedue to a molecular interaction between high apolipoprotein E (whichis seen in patients with the ε4 allele of APOE4) that resultsin a reduced BChE activity,50 as well asa possible synergistic effect of BCHE-K and APOE4 on the developmentof AD.51 This evidence concerns the gene BCHE and Alzheimer disease.