Genetic Polymorphism of Drug Metabolism in Humans

Increased genotype frequency of N‐acetyltransferase 2 slow acetylation in patients with rheumatoid arthritis

“…29 The susceptibility to RA is lower in populations with a preponderance of fast acetylators (90% in Japan and 80% in China) and higher in populations with a preponderance of slow acetylators (50% in Polish persons and 80% in Alaskan Indians). [34][35][36] The abovementioned data confirm that environmental factors play an important role in the pathogenesis of RA. The subjects with slow acetylation genotypes may be more at risk for RA development.…”

ChemInform Abstract: The Biochemistry of Drug Metabolism — An Introduction. Part 5. Metabolism and Bioactivity

“…As shown here, the metabolism of benzene (5.115) begins with a CYP2E1-catalyzed oxidation, yielding an unstable epoxide known as benzene oxide (5.116). 4.109 [2] [5]), leading to S-phenylmercapturic acid (5.119), a urinary biomarker for benzene exposure [196]. 7 min in blood and forms adducts with blood proteins [195].…”

“…3.68 [2] [4]) to yield 1,2-dihydrobenzene-1,2-diol (5.123). The main reaction of 5.116 is its fast and proton-catalyzed isomerization to phenol (5.126), another urinary marker of benzene exposure [196]. However, the in vivo significance of 5.124 awaits deeper assessment.…”

Glutathione S Transferase Theta 1 Gene (GSTT1) Null Genotype Is Associated with an Increased Risk for Acquired Aplastic Anemia in Children

“…The importance of GSTT1 in the protection of hematopoietic cells from environmental pollutants has been proven in a population exposed to 1,3-butadiene-the in vitro sister chromatid exchange in human lymphocytes in the presence of 1,3-butadiene was 16-fold higher in cells from individuals lacking the GSTT1 gene expression (55,56). With regard to benzene detoxification, which is highly important in context with AA, GSTT1 is a major protection factor of individual susceptibility to benzene-induced chromosomal damage (51) and induces the urinary excretion of benzene metabolites with higher excretion of t,tMA (57) . Proving a direct causative coincidence between exogenous pollutants and marrow failure is difficult because the onset of marrow failure cannot be dated accurately.…”