title: Molecular investigation of the functional relevance of missense variants of ICAM-1.
abstract: 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(241R); 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 approximately 150 min, whereas M2, M4, and M7 displayed a decreased half-life of approximately 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.
authors.affiliation: Leibniz-Institute for Arteriosclerosis Research, University of Muenster, Muenster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Vischer
authors.forename: Ralph
authors.initials: R
authors.lastname: Telgmann
authors.forename: Boris
authors.initials: B
authors.lastname: Schmitz
authors.forename: Sandra
authors.initials: S
authors.lastname: Hasenkamp
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmidt-Petersen
authors.forename: Katrin
authors.initials: K
authors.lastname: Beining
authors.forename: Andreas
authors.initials: A
authors.lastname: Huge
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand-Herrmann
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D018799:Intercellular Adhesion Molecule-1