TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects.
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.
Carlson
Christopher S
CS
Division of Public Health Sciences, The Fred Hutchinson Cancer Research Center, The University of Washington, Seattle, WA, USA.
Heagerty
Patrick J
PJ
Nord
Alex S
AS
Pritchard
David K
DK
Ranchalis
Jane
J
Boguch
Joshua M
JM
Duan
Hangjun
H
Hatsukami
Thomas S
TS
Schwartz
Stephen M
SM
Rieder
Mark J
MJ
Nickerson
Deborah A
DA
Jarvik
Gail P
GP
D000368:Aged; D000369:Aged, 80 and over; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D016893:Carotid Stenosis / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D020672:I-kappa B Proteins; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D020672:I-kappa B Proteins; D015850:Interleukin-6; C000606204:NFKBIA protein, human; D019948:Receptors, Interleukin-4; D000072000:NF-KappaB Inhibitor alpha; D005340:Fibrinogen; D001094:Arachidonate 5-Lipoxygenase