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Association of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study.
Tuesday,2012-11-06 12:18 America/Los_Angeles — eenright
| Title | Association of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Carty, CL, Heagerty, P, Heckbert, SR, Enquobahrie, DA, Jarvik, GP, Davis, S, Tracy, RP, Reiner, AP |
| Journal | J Atheroscler Thromb |
| Volume | 16 |
| Issue | 4 |
| Pagination | 419-30 |
| Date Published | 2009 Aug |
| ISSN | 1880-3873 |
| Keywords | Aged, Cardiovascular Diseases, Cholesterol, HDL, Cytokines, Female, Gene Regulatory Networks, Humans, Inflammation Mediators, Interleukin 1 Receptor Antagonist Protein, Interleukin-1beta, Interleukin-6, Male, Polymorphism, Single Nucleotide, Proportional Hazards Models, Serum Amyloid A Protein, Tumor Necrosis Factor-alpha, Tunica Intima |
| Abstract | <p><b>AIM: </b>Since inflammation is an important contributor to atherosclerosis, gene variants mediating inflammation are of interest. We investigated gene variants in acute phase serum amyloid-A (SAA), a sensitive indicator of inflammatory activity, and their associations with cardiovascular disease (CVD) and HDL cholesterol. Interaction of the SAA genes with genetic variants of their regulators, IL-1, IL-6 and TNF-alpha in influencing CVD was also explored.</p><p><b>METHODS: </b>SNPs characterizing common variation in the SAA1 and SAA2 genes were genotyped in European-(EA) and African-American (AA) participants (n=3969 and n=719) of the Cardiovascular Health Study. Using linear and Cox proportional hazards regression, we assessed associations of SNPs with baseline carotid artery intima-media thickness (cIMT) and risk of incident myocardial infarction, ischemic stroke, total CVD events or mortality during 14 years of follow-up.</p><p><b>RESULTS: </b>No associations between SAA SNPs and outcomes were observed in EA, with the exception of total CVD events; each rs4638289 minor allele was associated with an increased risk in obese individuals, HR=1.2 (95%CI: 0.981.4; p=0.086) and decreased risk among non-obese, HR=0.9 (95%CI: 0.80.99; p=0.026). In AA, we observed modest associations between SAA SNPs and cIMT, potentially modified by HDL. SAA SNPs were also associated with lower HDL in EA and AA. Suggestive gene-gene interaction findings for cIMT in AA and CVD mortality in EA were not significant in subsequent model selection tests.</p><p><b>CONCLUSION: </b>Associations of SAA SNPs with cIMT, HDL and total CVD events were identified, unadjusted for multiple testing. These findings should be regarded as hypothesis-generating until confirmed by other studies.</p> |
| Alternate Journal | J. Atheroscler. Thromb. |
| PubMed ID | 19729864 |
| PubMed Central ID | PMC2890297 |
| Grant List | T32 HL007902 / HL / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / 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-55222 / HC / NHLBI NIH HHS / United States N01 HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States T32 HL007902-01 / HL / 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 |