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Publication : Human Validation of Genes Associated With a Murine Atherosclerotic Phenotype.

First Author  Pasterkamp G Year  2016
Journal  Arterioscler Thromb Vasc Biol Volume  36
Issue  6 Pages  1240-6
PubMed ID  27079880 Mgi Jnum  J:249620
Mgi Id  MGI:5920624 Doi  10.1161/ATVBAHA.115.306958
Citation  Pasterkamp G, et al. (2016) Human Validation of Genes Associated With a Murine Atherosclerotic Phenotype. Arterioscler Thromb Vasc Biol 36(6):1240-6
abstractText  OBJECTIVE: The genetically modified mouse is the most commonly used animal model for studying the pathogenesis of atherosclerotic disease. We aimed to assess if mice atherosclerosis-related genes could be validated in human disease through examination of results from genome-wide association studies. APPROACH AND RESULTS: We performed a systematic review to identify atherosclerosis-causing genes in mice and carried out gene-based association tests of their human orthologs for an association with human coronary artery disease and human large artery ischemic stroke. Moreover, we investigated the association of these genes with human atherosclerotic plaque characteristics. In addition, we assessed the presence of tissue-specific cis-acting expression quantitative trait loci for these genes in humans. Finally, using pathway analyses we show that the putative atherosclerosis-causing genes revealed few associations with human coronary artery disease, large artery ischemic stroke, or atherosclerotic plaque characteristics, despite the fact that the majority of these genes have cis-acting expression quantitative trait loci. CONCLUSIONS: A role for genes that has been observed in mice for atherosclerotic lesion development could scarcely be confirmed by studying associations of disease development with common human genetic variants. The value of murine atherosclerotic models for selection of therapeutic targets in human disease remains unclear.
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