Genetic Determination of Acute Phase Reactant Levels: The Strong Heart StudyBest L.G.a · North K.E.b · Tracy R.P.c · Lee E.T.d · Howard B.V.e · Palmieri V.f · MacCluer J.W.g
aMissouri Breaks Industries Research Inc, Timber Lake, S.Dak., bUniversity of North Carolina, Chapel Hill,N.C., cLaboratory for Clinical Biochemistry Research, University of Vermont, Burlington, Vt., dUniversity of Oklahoma Health Sciences Center, Oklahoma City, Okla., eMedstar Research Institute, Washington, D.C., fWeill Medical College of Cornell University, New York, N.Y., and gSouthwest Foundation for Biomedical Research, SanAntonio,Tex., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Objective: C-reactive protein (CRP), fibrinogen and plasminogen activating inhibitor-1 (PAI-1) are acute phase reactants (APRs); and high levels are indicative of physiologic inflammatory responses. Basal (non-stimulated) APR levels have also been shown to predict atherosclerotic complications in a number of populations. We sought to determine the relative contributions of genetic and environmental factors influencing basal serum levels of APRs. Methods: This study used univariate quantitative genetic analyses to partition the phenotypic variance of these APRs into their additive genetic and environmental components using maximum likelihood variance decomposition methods. Bivariate analyses were done to detect genetic correlation between APRs. The computer program SOLAR was used to perform these analyses. Results: The Strong Heart Study (SHS) includes information on approximately 1,294 American Indian relative pairs. The proportion of variance due to environmental and acquired covariates affecting these APRs was modest, ranging from 16–20%. The proportion of variance due to genetic factors (heritability) ranged from 24–46%. In addition, there were significant genetic correlations between CRP/fibrinogen (ρ = 0.41 ± 0.12) and CRP/PAI-1 (ρ = 0.46 ± 0.19); but not between fibrinogen/PAI-1. Conclusion: In the SHS cohort, the levels of APRs are determined to a substantial degree by genetic influences, and CRP shares common genetic determinants with fibrinogen and PAI-1.
© 2004 S. Karger AG, Basel
- Ridker PM: Novel risk factors and markers for coronary disease. Adv Intern Med 2000;45:391–418.
- Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V: C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004;350:1387–1397.
- Kohler HP, Grant PJ: Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med 2000;342:1792–1801.
- Pankow JS, Folsom AR, Cushman M, Borecki IB, Hopkins PN, Eckfeldt JH, Tracy RP: Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis 2001;154:681–689.
- Vickers MA, Green FR, Terry C, Mayosi BM, Julier C, Lathrop M, Ratcliffe PJ, Watkins HC, Keavney B: Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002;53:1029–1034.
- Pankow JS, Folsom AR, Province MA, Rao DC, Williams RR, Eckfeldt J, Sellers TA: Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels in the NHLBI family heart study. Arterioscler Thromb Vasc Biol 1998;18:1559–1567.
- Henry M, Tregouet DA, Alessi MC, Aillaud MF, Visvikis S, Siest G, Tiret L, Juhan-Vague I: Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations: a family study with part of the Stanislas Cohort. Arterioscler Thromb Vasc Biol 1998;18:84–91.
- Freeman MS, Mansfield MW, Barrett JH, Grant PJ: Genetic contribution to circulating levels of hemostatic factors in healthy families with effects of known genetic polymorphisms on heritability. Arterioscler Thromb Vasc Biol 2002;22:506–510.
Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG: Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation 1996;94:2057–2063.
- Ford ES, Giles WH: Serum C-reactive protein and fibrinogen concentrations and self-reported angina pectoris and myocardial infarction: Findings from National Health and Nutrition Examination Survey III. J Clin Epidemiol 2000;53:95–102.
- Lee ET, Welty TK, Fabsitz R, Cowan LD, Le NA, Oopik AJ, Cucchiara AJ, Savage PJ, Howard BV: The Strong Heart Study. A study of cardiovascular disease in American Indians: design and methods. Am J Epidemiol 1990;132:1141–1155.
- Macy EM, Hayes TE, Tracy RP: Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem 1997;43:52–58.
- Declerck PJ, Alessi MC, Verstreken M, Kruithof EK, Juhan-Vague I, Collen D: Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood 1988;71:220–225.
- Geffken DF, Keating FG, Kennedy MH, Cornell ES, Bovill EG, Tracy RP: The measurement of fibrinogen in population-based research. Studies on instrumentation and methodology. Arch Pathol Lab Med 1994;118:1106–1109.
- Almasy L, Blangero J: Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 1998;62:1198–1211.
- Howard BV, Lee ET, Cowan LD, Devereux RB, Galloway JM, Go OT, Howard WJ, Rhoades ER, Robbins DC, Sievers ML, Welty TK: Rising tide of cardiovascular disease in American Indians. The Strong Heart Study. Circulation 1999;99:2389–2395.
- Lowe GD, Yarnell JW, Rumley A, Bainton D, Sweetnam PM: C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: Are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001;21:603–610.
- North KE, Howard BV, Welty TK, Best LG, Lee ET, Yeh JL, Fabsitz RR, Roman MJ, MacCluer JW: Genetic and environmental contributions to cardiovascular disease risk in American Indians: the strong heart family study. Am J Epidemiol 2003;157:303–314.
- Becker TM, Wiggins C, Peek C, Key CR, Samet JM: Mortality from infectious diseases among New Mexico’s American Indians, Hispanic whites, and other whites, 1958–87. Am J Public Health 1990;80:320–323.
Howard BV, Welty TK, Fabsitz RR, Cowan LD, Oopik AJ, Le NA, Yeh J, Savage PJ, Lee ET: Risk factors for coronary heart disease in diabetic and nondiabetic Native Americans: The Strong Heart Study. Diabetes 1992;41(suppl 2):4–11.
- Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, Sakkinen PA, Tracy RP: Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999;100:717–722.
- Weyer C, Yudkin JS, Stehouwer CD, Schalkwijk CG, Pratley RE, Tataranni PA: Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians. Atherosclerosis 2002;161:233–242.
- Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL: Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab 2003;88:255–259.
- Ando R, Doi M, Yamauchi K, Chida Y, Ida T, Endo K, Yanagi H, Tomura S: Association of beta-fibrinogen and factor VII polymorphism with plasma fibrinogen and factor VII levels, and no association of PAI-1 polymorphism with plasma PAI-1 levels in hemodialysis patients. Clin Nephrol 2002;58:25–32.
- Szalai AJ, McCrory MA, Cooper GS, Wu J, Kimberly RP: Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene. Genes Immun 2002;3:14–19.
- Wolford JK, Gruber JD, Ossowski VM, Vozarova B, Antonio Tataranni P, Bogardus C, Hanson RL: A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab 2003;78:136–144.
- de Maat MP, Bladbjerg EM, Johansen LG, de Knijff P, Gram J, Kluft C, Jespersen J: DNA-polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit – is there a relation with the low risk of cardiovascular disease in the Inuit? Thromb Haemost 1999;81:547–552.
- Festa A, D’Agostino R Jr, Rich SS, Jenny NS, Tracy RP, Haffner SM: Promoter (4G/5G) plasminogen activator inhibitor-1 genotype and plasminogen activator inhibitor-1 levels in blacks, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study. Circulation 2003;107:2422–2427.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.