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

Christopher S. Carlson, Patrick J. Heagerty, Alexander Nord, David K. Pritchard, Jane Ranchalis, Joshua M. Boguch, Hangjun Duan, Thomas S. Hatsukami, Stephen M. Schwartz, Mark J. Rieder, Deborah A. Nickerson, Gail P. Jarvik

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalHuman Genetics
Volume121
Issue number1
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Carlson, C. S., Heagerty, P. J., Nord, A., Pritchard, D. K., Ranchalis, J., Boguch, J. M., Duan, H., Hatsukami, T. S., Schwartz, S. M., Rieder, M. J., Nickerson, D. A., & Jarvik, G. P. (2007). TagSNP evaluation for the association of 42 inflammation loci and vascular disease: Evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects. Human Genetics, 121(1), 65-75. https://doi.org/10.1007/s00439-006-0289-8