| Polymorphisms predicted to alter function in prostaglandin E2 synthase and prostaglandin E2 receptors. | |
| | |
MedLine Citation:
|
PMID: 17460551 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND AND OBJECTIVE: Prostaglandin synthesis is the primary target of aspirin and other nonsteroidal antiinflammatory drugs, and thus is a pathway of major interest to pharmacology, pharmacogenetics, and epidemiology. Several lines of evidence implicate prostaglandin E2 in carcinogenesis; this study aimed to identify genetic variants in genes related to prostaglandin E2 synthesis and signaling. METHODS: We resequenced the coding regions of human prostaglandin E2 synthase (PGES), and prostaglandin E2 receptors EP1, EP2, and EP4 in 48 African-Americans and 47 Caucasians. RESULTS AND CONCLUSIONS: We identified 23 variants, 6 of which cause amino acid changes. The non-synonymous polymorphisms in PGES, EP1, and EP2 were present only among African-Americans; both populations carried non-synonymous polymorphisms in EP4. We used two sequence homology-based programs, SIFT and PolyPhen, to predict the impact of these polymorphisms. These programs predicted that the amino-acid changes p.Phe119Val in EP1, p.Ala44Glu in EP2, and possibly p.Val7Glu in PGES, p.Thr176Ile in EP4 and p.Gly420Asp in EP4 are likely to affect protein function. Thus, these variants may be relevant for inflammatory conditions, carcinogenesis, and pharmacogenetics. |
| | |
Authors:
|
Jeannette Bigler; Justin G Sibert; Elizabeth M Poole; Christopher S Carlson; John D Potter; Cornelia M Ulrich |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Pharmacogenetics and genomics Volume: 17 ISSN: 1744-6872 ISO Abbreviation: Pharmacogenet. Genomics Publication Date: 2007 Mar |
Date Detail:
|
Created Date: 2007-04-26 Completed Date: 2007-05-18 Revised Date: 2007-12-03 |
Medline Journal Info:
|
Nlm Unique ID: 101231005 Medline TA: Pharmacogenet Genomics Country: United States |
Other Details:
|
Languages: eng Pagination: 221-7 Citation Subset: IM |
Affiliation:
|
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. jbigler@amgen.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
African Continental Ancestry Group
/
genetics Amino Acid Substitution Base Sequence European Continental Ancestry Group / genetics Forecasting Gene Frequency Humans Intramolecular Oxidoreductases / genetics*, physiology Polymorphism, Genetic* Receptors, Prostaglandin E / genetics*, physiology Sequence Analysis, Protein / methods Sequence Homology, Amino Acid Software Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
|
R01 CA 89445/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Receptors, Prostaglandin E; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.3/prostaglandin-E synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Common ABCB1 polymorphisms are not associated with multidrug resistance in epilepsy using a gene-wid...
Next Document: Fish oil treatment for kidney transplant recipients: a meta-analysis of randomized controlled trials...