Do similar genetic factors predispose patients to develop DILE and SLE?
The genetic risk factors in DILE and idiopathic SLE appear to be quite separate. The major risk for procainamide- or hydralazine-induced lupus appears to be acetylator phenotype. Metabolism of these drugs involves the hepatic enzyme N-acetyltransferase, which catalyzes the acetylation of amine or hydrazine groups. The rate at which this reaction takes place is under genetic control. Approximately 50% of the US white population is fast acetylators, with the rest being slow acetylators. The slow acetylators, when treated with procainamide or hydralazine, develop ANAs earlier and at higher titers and are more likely to develop symptomatic disease than fast acetylators. Despite its chemical similarity to procainamide and its similar drug action, N-acetylprocainamide has not been associated with drug-induced ANA production or DILE. In idiopathic SLE, acetylator phenotype does not appear to be involved in genetic susceptibility. Instead, human leukocyte antigen (HLA) class II genes, complement deficiencies, and multiple other genes are important in the complex genetic basis of SLE (Systemic Lupus Erythematosus). HLA-DR4 and null gene for C4 may contribute to the risk of developing hydralazine-induced DILE.