title: Cyclooxygenase 1 (COX1) polymorphisms in African-American and Caucasian populations.
abstract: Cyclooxygenases (COXs) are the primary targets of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), and thus enzymes of major interest to pharmacology, pharmacogenetics, and epidemiology. Genetic variants that affect enzyme function, or the interaction with NSAIDs, could alter drug response. We have screened the human COX1 gene coding regions of 48 African-American and 47 Caucasian individuals using DNA sequencing. We identified 13 coding-region variants, of which seven were amino-acid substitutions, and further five intronic polymorphisms within 60bp of an exon. All nonsynonymous variants were confirmed in an independent Caucasian population (n=94 unrelated individuals). Most of the discovered polymorphisms were rare, although some variants resulting in amino-acid changes occurred at appreciable frequency in at least one population (> or =4%: R8W, P17L, L237M). We used two sequence-homology-based software programs to predict the potential impact of these polymorphisms on COX1 function. The L237M substitution was predicted as most likely to alter protein function, whereas the glycine at position 230 may be specific to COX1 function. More detailed phenotypic characterizations of these COX1 polymorphisms remain to be undertaken.
authors.affiliation: Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, University of Washington, Seattle, WA 98109-1024, USA. nulrich@fhcrc.org
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Jeannette
authors.initials: J
authors.lastname: Bigler
authors.forename: Justin
authors.initials: J
authors.lastname: Sibert
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Greene
authors.forename: Rachel
authors.initials: R
authors.lastname: Sparks
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
mesh_terms: D019943:Amino Acid Substitution; D044383:Black People / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D051545:Cyclooxygenase 1; D005091:Exons; D006801:Humans; D007438:Introns; D007527:Isoenzymes / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins; D011110:Polymorphism, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000502:physiology; D020539:Sequence Analysis, Protein; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases