Altered Distribution of the Debrisoquine Oxidative Phenotypes in Children with Type 1 Diabetes mellitus

Abstract

Objective: The recently observed increase in the incidence of type 1 diabetes mellitus (Type 1 DM) suggests a major role of environmental factors in the etiopathogenesis of the disease. The individual variation in cytochrome P₄₅₀IID6 may influence the individual susceptibility to environmentally linked diseases. We aimed to evaluate the prevalence of cytochrome P₄₅₀IID6 phenotypes in Hungarian children with Type 1 DM (n = 69) compared to healthy controls (n = 100). Methods: Debrisoquine was administered orally and debrisoquine hydroxylation phenotype was determined as a metabolic ratio of urinary recovered debrisoquine and 4-hydroxydebrisoquine. Results: Eight of the 100 healthy subjects (8%) and 15 of the 69 diabetic children (22%) (p < 0.05) had cytochrome P₄₅₀IID6 poor metabolizer phenotype (metabolic ratio ≧12.6). Conclusion: Cytochrome P₄₅₀IID6’s activity may play a role in the development of Type 1 DM.

Gene–environment interactions in sporadic Parkinson's disease

“…This phenotype is termed poor metabolizer, and has been associated with various diseases and/or susceptibility syndromes (Roddam et al . 2000; Madacsy et al . 2004).…”

“…The homozygous presence of defective CYP2D6 alleles leads to a total absence of active enzyme and an impaired ability to metabolize xenobiotics. This phenotype is termed poor metabolizer, and has been associated with various diseases and/or susceptibility syndromes (Roddam et al 2000;Madacsy et al 2004).…”