Journal
PHARMACOGENETICS AND GENOMICS
Volume 18, Issue 11, Pages 1017-1019Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e32830d32ad
Keywords
cardiovascular disease; functional analyses; intercellular adhesion molecule-1; missense variants
Funding
- German Ministry for Education and Science (BMBF) [0313040C]
- Else Kroner-Fresenius foundation [P27/05//A24/05//F01]
- Interdisziplinares Zentrum fur Klinische Forschung [Bra1/001/08]
- Deutsche Forschungsgemeinschaft [Br1589/8-1]
- EU-NoE [FP6-2005-LIFESCIHEALTH-6]
- ICT [FP7-ICT-2007-2]
- VPH2 [224635]
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In genome-wide studies, the intercellular adhesion molecule-1 (ICAM-1) locus has been associated with cardiovascular and inflammatory bowel diseases. To determine the functional relevance of five missense ICAM-1 variants (G241R; I316V; P352L; K469E; R478W), we generated wild-type and variant proteins [M2(241 R); M3(469E); M4(352L); M5(478W); M6(316V); M7(352L/ 469E)] and transiently transfected CV1 cells. Reverse transcription PCR, western blot, and ELISA did not reveal any differences in mRNA and protein expression levels for any construct. Conversely, in pulse-chase experiments, compared with wild-type (90-120 min), M3 and M5 possessed a prolonged half-life of similar to 150 min, whereas M2, M4, and M7 displayed a decreased half-life of similar to 60-75 min, implying differences in protein degradation. Our results do not indicate a major impact of missense variants on ICAM-1 biological function, even if G241R and K469E were functional in pulse-chase experiments. Whether these differences in protein stability exert measurable functional consequences needs to be elucidated further. Pharmacogenetics and Genomics 18:1017-1019 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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