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TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects

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Abstract

Inflammatory markers have consistently been associated with vascular disease. Evidence of genetic polymorphisms in inflammatory loci that predict severe carotid artery disease (CAAD) would suggest that this relationship is not secondary to other correlated factors, but related to inflammation itself. We examined the full common genetic variation in 42 inflammatory loci for prediction of severe CAAD versus ultrasound proven controls using a tagSNP approach. For selected loci, monocyte RNA levels were contrasted in subjects with and without CAAD. We confirm the association of IL6−174, FGB −455, and ALOX5 with CAAD and show that multiple ALOX5 SNPs independently predict CAAD. We provide evidence for previously unreported associations of SNPs in IL4R, NFKBIA, and PLG with CAAD, and weaker evidence for associations with CSF3, IL10RA, and VCAM1. The NFKBIA and IL10RA expression levels significantly differed between subjects with CAAD and controls. These results support a role for genetic variation related to inflammation in CAAD and a causal role for specific gene products.

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Acknowledgments

This work was funded by the National Institutes of Health (NIH) RO1 HL074366, with additional support from NIH R01HL67406, P01 HL072262, R01 HL073401, and the Veteran Affairs Epidemiology Research and Information Center Program (award CSP 701S). We utilized public resequencing data from the SeattleSNPs program, supported by NIH U01 HL66682 (http://www.pga.gs.washington.edu/).

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Correspondence to Gail P. Jarvik.

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Carlson, C.S., Heagerty, P.J., Nord, A.S. et al. TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects. Hum Genet 121, 65–75 (2007). https://doi.org/10.1007/s00439-006-0289-8

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  • DOI: https://doi.org/10.1007/s00439-006-0289-8

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