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Interaction between fibrinogen and IL-6 genetic variants and associations with cardiovascular disease risk in the Cardiovascular Health Study.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Interaction between fibrinogen and IL-6 genetic variants and associations with cardiovascular disease risk in the Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Carty, CL, Heagerty, P, Heckbert, SR, Jarvik, GP, Lange, LA, Cushman, M, Tracy, RP, Reiner, AP |
| Journal | Ann Hum Genet |
| Volume | 74 |
| Issue | 1 |
| Pagination | 1-10 |
| Date Published | 2010 Jan |
| ISSN | 1469-1809 |
| Keywords | Aged, Cardiovascular Diseases, Carotid Arteries, Female, Fibrinogen, Genetic Predisposition to Disease, Genetic Variation, Humans, Interleukin-6, Male, Models, Biological, Myocardial Infarction, Polymorphism, Single Nucleotide, Risk, Stroke |
| Abstract | <p>The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) and subsequent impact on cardiovascular disease (CVD) risk is not well-studied. We investigated joint associations of fibrinogen and IL6 tagSNPs with fibrinogen concentrations, carotid intima-media thickness, and myocardial infarction or ischemic stroke in 3900 European-American Cardiovascular Health Study participants. To identify combinations of genetic main effects and interactions associated with outcomes, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen and IL6 SNPs were significantly associated with fibrinogen level (p < 0.005), but not with other outcomes. Fibrinogen levels were higher in individuals having FGB1437 (rs1800790) and lacking FGA6534 (rs6050) minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen level. Marginally significant (p= 0.03) interactions between IL-6 level and FGA and FGG promoter SNPs associated with fibrinogen levels were detected. We identified potential gene-gene interactions influencing fibrinogen levels. Although IL-6 responsive binding sites are present in fibrinogen gene promoter regions, we did not find strong evidence of interaction between fibrinogen SNPs and IL6 SNPs or levels influencing CVD.</p> |
| DOI | 10.1111/j.1469-1809.2009.00551.x |
| Alternate Journal | Ann. Hum. Genet. |
| PubMed ID | 20059469 |
| PubMed Central ID | PMC2946374 |
| Grant List | R01 HL071862-05A1 / HL / NHLBI NIH HHS / United States T32 HL007902 / HL / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States U01 HL080295-01 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States R01 HL071862 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States T32 HL007902-10 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States |