Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus

Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4-hydroxydebrisoquine, is catalyzed by a discrete isozyme of cytochrome P-450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, "poor metabolizers" and "extensive metabolizers," discernible in the normal population. We observed the poor metabolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P less than 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metabolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE.