Molecular diversity at the CYP2D6 locus in the Mediterranean region

Eur J Hum Genet. 2004 Nov;12(11):916-24. doi: 10.1038/sj.ejhg.5201243.


Despite the importance of cytochrome P450 in the metabolism of many drugs, several aspects of molecular variation at one of the main loci coding for it, CYP2D6, have never been analysed so far. Here we show that it is possible to rapidly and efficiently genotype the main European allelic variants at this locus by a SNaPshot method identifying chromosomal rearrangements and nine single-nucleotide polymorphisms. Haplotypes could be reconstructed from data on 494 chromosomes in six populations of the Mediterranean region. High levels of linkage disequilibrium were found within the chromosome region screened, suggesting that CYP2D6 may be part of a genomic recombination block, and hence that, aside from unequal crossingover that led to large chromosomal rearrangements, its haplotype diversity essentially originated through the accumulation of mutations. With the only, albeit statistically insignificant, exception of Syria, haplotype frequencies do not differ among the populations studied, despite the presence among them of three well-known genetic outliers, which could be the result of common selective pressures playing a role in shaping CYP2D6 variation over the area of Europe that we surveyed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochrome P-450 CYP2D6 / genetics*
  • Gene Frequency
  • Genetic Variation*
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Mediterranean Region
  • Physical Chromosome Mapping
  • Polymorphism, Single Nucleotide


  • Cytochrome P-450 CYP2D6

Associated data

  • OMIM/124030