التفاصيل البيبلوغرافية
| العنوان: |
Hematopoietic prostaglandin D synthase (HPGDS): A high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer |
| المؤلفون: |
Alicia M. Materi, Shiv Kapoor, John M. Lin, Amy M. Lin, Robert W. Haile, Jae Man Park, Henry J. Lin, Julie E. Goodman, Temitope O. Keku, Laurence N. Kolonel, R. Michael Garavito, Wonhwa Cho, Aihua Dai, Leah B. Sansbury, Sudipto Das, A. Joan Levine, Ruth E. Patterson, Tsuyoshi Inoue, Brigette L. Tippin, Robert S. Sandler, John A. Lawson, Loic Le Marchand, Wen-Liang Song, Alan M. Kwong, Rowan T. Chlebowski |
| بيانات النشر: |
The University of North Carolina at Chapel Hill University Libraries, 2012. |
| سنة النشر: |
2012 |
| مصطلحات موضوعية: |
Adult, Models, Molecular, medicine.medical_specialty, Physiology, Colorectal cancer, Protein Conformation, Prostaglandin, Lipocalin, Biology, Biochemistry, Isozyme, Article, chemistry.chemical_compound, Gene Knockout Techniques, Mice, Valine, Internal medicine, Enzyme Stability, medicine, Animals, Humans, Genetic Predisposition to Disease, Transgenes, Pharmacology, Case-control study, Cell Biology, Odds ratio, medicine.disease, PLA2G4A, Lipocalins, Black or African American, Intramolecular Oxidoreductases, Isoenzymes, Endocrinology, chemistry, Amino Acid Substitution, Case-Control Studies, Cancer research, biology.protein, Colorectal Neoplasms |
| الوصف: |
Intestinal tumors in ApcMin/+ mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D2 (PGD2). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37 °C, the wild-type enzyme lost 15% of its activity in one hour, whereas the Val187Ile form remained >95% active. At 50 °C, the half life of native HPGDS was 9 minutes, compared to 42 minutes for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75–1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model. |
| اللغة: |
English |
| DOI: |
10.17615/d058-1994 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f937b02e5c963ba5f4d31819d4d898b |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....4f937b02e5c963ba5f4d31819d4d898b |
| قاعدة البيانات: |
OpenAIRE |