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01 September 1998

Increased frequency of defected CYP2D6 gene alleles among children with leukemia in comparison to children with infectious diseases and atopic allergy

Elżbieta Zielińska, Henryk W. Witas, Jerzy Bodalski

Med Sci Monit 1998; 4(5): BR756-764 :: ID: 501961

Abstract

The aim of this study was to evaluate the frequency of CYP2D6 gene mutations in Polish children as well as to determine the significance of genotypes encoding poor metabolizer phenotypes in chronic diseases such as atopic allergy and lympho-myeloproliferative diseases. Out of 172 children of which 94 had been treated for acute infectious diseases, 57 presented with atopic allergy and 21 with lympho-myeloproliferative diseases. We isolated DNA from peripheral blood. We identified by means of the allele-specific amplification assay (ASA) followed by analysis of restriction fragment length polymorphism the presence of A 2367 deletion in exon 5 (allele D6-A) and G1934→A transition replacing the junction between intron 3 and exon 4 (allele D6-B), in the CYP2D6 gene. This method allows for the detection of genotypes encoding cytochrome P4502D6 (presence of allele wt) and identifies poor metabolizers which are homozygous or heterozygous for defective D6-A and D6-B alleles. In 5.0% of the studied children we noted genotypes with two defective alleles, which reflects the occurrence of poor metabolizers in other parts of Europe. The frequency of mutations and distribution of genotypes in children with allergies is comparable to results obtained from the control group. However, in children with lymphoproliferative diseases and positive family history of neoplasms, mutated alleles appear statistically significantly more frequently (p< 0.0003). In these children genotypes encoding metabolic defects were identified twice as frequently. The identification of CYP2D6 gene mutations may be useful in the determination of risk factors such as the genetic predisposition to lympho-myeloproliferative diseases.

Keywords: mono-oxygenase cytochrome P450, genotype CYP2D6, children, Allergy, Leukemia

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750