Populations and genetic polymorphisms

Mol Diagn. 1999 Dec;4(4):299-307. doi: 10.154/MODI00400299.


Population frequencies of many polymorphic genes of pharmacogenetic interest depend on race or ethnic specificity. Association of these genes with person-to-person differences in drug effectiveness (hypersensitivity or resistance) and drug toxicity may also depend on the racial or ethnic characteristics of a population. Information about ethnic specificity is an integral part of pharmacogenetics because it can suggest a starting point for further study of these traits, tailoring drug therapy to the individual patient, and rational development and clinical trials of new drugs. Ethnic specificities of several medically important metabolic traits serve to illustrate these ideas. Among the traits considered is primaquine sensitivity, a sex-linked trait attributed to glucose-6-phosphate dehydrogenase deficiency that mainly affects males among African, Mediterranean, and Oriental people. Additional examples include the remarkable sensitivity of the Japanese to alcohol (ethanol) compared with whites; the ethnic specificity of the cytochrome P-450 enzyme CYP2D6* (debrisoquine/sparteine) polymorphism that results in poor, extensive, and ultrarapid metabolizers of at least 30 drugs; the CYP2C19* (mephenytoin) polymorphism that accounts for variable metabolism of proguanil, omeprazole, and certain barbiturates; and the polymorphic (NAT2*) acetylation of hydrazine and aromatic amine drugs, such as isoniazid, hydralazine, and sulfasalazine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aryl Hydrocarbon Hydroxylases*
  • Arylamine N-Acetyltransferase / genetics
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • Genetics, Population*
  • Glucosephosphate Dehydrogenase / genetics
  • Humans
  • Mixed Function Oxygenases / genetics
  • Pharmaceutical Preparations / metabolism
  • Pharmacogenetics*
  • Phylogeny
  • Polymorphism, Genetic*
  • Racial Groups / genetics


  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Glucosephosphate Dehydrogenase
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Arylamine N-Acetyltransferase