Possible Role of Cytochromes P450 in Lupus Erythematosus and Related Disorders

Abstract

Cytochromes P450 comprise a superfamily of enzymes pivotal in the metabolism of innumerable substrates of both endogenous and exogenous origin. The total number of distinct P450 genes, each encoding a different enzyme in humans, is estimated to be at least 60 and possibly several hundred. The cytochrome P450 (CYP) superfamily nomenclature system is based on divergent evolution of the genes. Most of the enzymes within gene families CYP1, CYP2, CYP3 and CYP4 appear to have evolved as the body's primary defense against the onslaught of chemicals confronted on a daily basis. Whereas P450 enzymes more than 3.5 billion years ago were undoubtedly designed as necessary components of signal transduction pathways, in the past billion years most P450 enzymes have become generally responsible for the detoxification of numerous foreign chemicals. During such oxidative metabolism, it has become increasingly apparent that these enzymes are also capable of functioning in an ambivalent manner, generating toxic intermediates. More than a dozen human P450 polymorphisms have been characterized. Genetic variability in P450 expression is therefore likely to have significant bearing on individual susceptibility to chemical toxicity. In this review, genetic differences in human P450 expression are outlined, and their possible relationship to autoimmune disease is examined. In addition, the speculative role of P450 polymorphisms in several 'lupus-like' disorders is discussed.

Single-nucleotide polymorphisms and haplotype of CYP2E1gene associated with systemic lupus erythematosus in Chinese population

“…Xenobiotic exposures often trigger the onset of autoimmune diseases including SLE, human CYP genes have significant bearing on individual susceptibility to chemical toxicity and were speculated to be involved in several 'lupus-like' disorders [32]. The inactive CYP2D6*4A allele may be a contributory factor for SLE [33].…”

Cytochrome P450 polymorphisms in patients with Behcet's disease

“…Cytochrome P‐450 polymorphism has been linked to susceptibility to certain autoimmune diseases such as systemic lupus erythematosus (SLE) and scleroderma 7,8 . In addition, circulating plasma concentrations of pro‐inflammatory cytokines (e.g.…”

Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report

“…Other risk factors include the human leukocyte antigen (HLA)-DR4 genotype, slow hepatic acetylation and the null gene for C4 [7]. The mechanism or mechanisms for hydralazine-induced AAV is not fully understood but might be multifactorial.…”