Differential association between human prostacyclin receptor polymorphisms and the development of venous thrombosis and intimal hyperplasia: a clinical biomarker study
| Autor: | Scott Gleim, John Hwa, Kent Sierra, Min Ding, Ryan J. Horvath, Stefania Tacconelli, Valeria Moretta, Maria Domenica Guglielmi, Luigia Di Francesco, Jeremiah Stitham, Giovanna Baccante, Paola Patrignani, Karen Douville, Concetta Di Febbo, Marta L. Capone, Ettore Porreca |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Intimal hyperplasia Genetic Linkage Prostacyclin Receptors Epoprostenol Polymorphism Single Nucleotide Von Willebrand factor Internal medicine Genetics medicine Humans Platelet Genetic Testing Platelet activation General Pharmacology Toxicology and Pharmaceutics Molecular Biology Prostacyclin receptor Genetics (clinical) Aged Venous Thrombosis Hyperplasia biology business.industry Middle Aged Platelet Activation medicine.disease Thrombosis Thromboxane B2 P-Selectin Venous thrombosis Endocrinology biology.protein Molecular Medicine Female Tunica Intima business Biomarkers medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics. 18:611-620 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0b013e328301a774 |
| Popis: | Objective and methods The role of prostacyclin in the development of venous thrombosis and vascular dysfunction in humans is unclear. In patients with deep vein thrombosis (DVT, n=34) and controls (matched for age, sex, indexes of systemic inflammation and metabolic status, n=20), we studied (i) differences on systemic markers of vascular disease and platelet activation and (ii) the influence of prostacyclin receptor gene (PTGIR) polymorphisms. Main results Enhanced levels of urinary 11 -dehydro-thromboxane (TX)B 2 and plasma [soluble(s)] P-selectin, mostly platelet derived, were detected in DVT patients, whereas plasma von Willebrand factor levels and intima-media thickness of the common carotid arteries were not significantly different. In all patients' cohorts, we identified five PTGIR polymorphisms (three nonsynonymous: P226T, R212C, V196L; two synonymous: V53V, S328S). In the four individuals carriers of R212C polymorphism (three in DVT, one in controls), intima-media thickness values were significantly (P= 0.0043) higher than those detected in individuals of all cohorts [1.68 ±0.38, 1.55 (1.4-2.2) vs. 1.05 ± 0.33, 1.08 (0.01 -1.68) mm, respectively, mean ± SD, median (range)]. Moreover, enhanced sP-selectin and 11-dehydro.TXB 2 , in DVT versus controls, were statistically significant only in carriers of both synonymous PTGIR polymorphisms V53V/S328S. Only the PTGIR mutant R212C was dysfunctional when examined in an in vitro overexpression system. Conclusion Our results suggest a propensity of enhanced platelet activation in DVT patients with PTGIR polymorphisms V53V/S328S. Moreover, we identified a dysfunctional PTGIR polymorphism (R212C) associated with intimal hyperplasia. |
| Databáze: | OpenAIRE |
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