Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Summary for Patients (PDF)    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Sethi, A. A.    Nordestgaard, B. G.    Related Articles in PubMed    PubMed Citation    PubMed

ARTICLE

Angiotensinogen Mutations and Risk for Ischemic Heart Disease, Myocardial Infarction, and Ischemic Cerebrovascular Disease: Six Case–Control Studies from the Copenhagen City Heart Study

Amar A. Sethi, MD; Anne Tybjærg-Hansen, MD, DMSc; Marie-Louise Moes Grønholdt, MD, PhD; Rolf Steffensen, MD; Peter Schnohr, MD; and Børge G. Nordestgaard, MD, DMSc

15 May 2001 | Volume 134 Issue 10 | Pages 941-954

Background: The M235T and T174M angiotensinogen mutations have been linked to increased risk for ischemic heart and cerebrovascular disease.

Objective: To determine whether angiotensinogen mutations are associated with ischemic heart disease, myocardial infarction, and ischemic cerebrovascular disease.

Design: Six case–control studies from the Copenhagen City Heart Study.

Setting: Copenhagen, Denmark.

Participants: Participants in the Copenhagen City Heart Study and patients from the same hospital with ischemic heart disease (n = 866 and n = 943, respectively), myocardial infarction (n = 519 and n = 493, respectively), or ischemic cerebrovascular disease (n = 489 and n = 434, respectively) and 7975 controls without these conditions.

Measurements: Genotypes for the M235T and T174M angiotensinogen mutations were compared between controls and Copenhagen City Heart Study participants with ischemic heart disease, myocardial infarction, and cerebrovascular disease (studies 1a, 1b, and 1c) and patients from Copenhagen University Hospital with the same conditions (studies 2a, 2b, and 2c).

Results: Relative allele frequencies of 235T and 174M in the general population were 0.41 and 0.12, respectively. Genotype was not associated with increased risk for ischemic heart or ischemic cerebrovascular disease in studies of either mutation alone or combined in women or men. Among compound heterozygotes (235MT/174TM), women in case–control study 2a had decreased risk for ischemic heart disease in age-adjusted analysis; however, this decreased risk was not seen in multifactorial-adjusted or matched analyses, in men, or in case–control study 1a. Among double homozygotes (235TT/174MM), women in case–control study 2b had increased risk for myocardial infarction in matched analysis; however, this increased risk was not seen in age- or multifactorial-adjusted analyses, in men, or in case–control study 1b. Among single homozygotes (235TT/174TT), men in case–control study 2b had increased risk for myocardial infarction in multifactorial-adjusted and matched analyses. This risk was not present in age-adjusted analysis, in women, or in case–control study 1b. In addition, male single homozygotes had decreased risk for ischemic cerebrovascular disease in case–control study 2c in age- and multifactorial-adjusted analyses, but this finding was not seen in matched analysis, in women, or in case–control study 1c.

Conclusions: In six large case–control studies, the M235T and T174M angiotensinogen mutations were not consistently associated with increased (or decreased) risk for ischemic heart disease, myocardial infarction, or ischemic cerebrovascular disease. Statistically significant associations may represent chance findings rather than real phenomena.

Author and Article Information

From Herlev University Hospital, Copenhagen University Hospital, and Bispebjerg University Hospital, Copenhagen, Denmark.

Grant Support: By the Danish Heart Foundation, the Danish Medical Research Council, University of Copenhagen, the European Organization for the Control of Circulatory Diseases, the Beckett Fund, Manufacturer Frands Køhler Nielsen and Wife's Grant, and King Christian the Xth Fund.

Acknowledgment: The authors thank Marianne Lodahl for technical assistance and the participants of the Copenhagen City Heart Study for their willingness to participate.

Requests for Single Reprints: Børge G. Nordestgaard, MD, DMSc, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; e-mail, brno{at}herlevhosp.kbhamt.dk.

Current Author Addresses: Drs. Sethi and Nordestgaard: Department of Clinical Biochemistry 54M1, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.

Dr. Tybjærg-Hansen: Department of Clinical Biochemistry KB3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

Dr. Grønholdt: Department of Vascular Surgery, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

Dr. Steffensen: Department of Medicine B, Division of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø , Denmark.

Dr. Schnohr: The Copenhagen City Heart Study, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.

Author Contributions: Conception and design: A.A. Sethi, A. Tybjærg-Hansen, M.L.M. Grønholdt, R. Steffensen, P. Schnohr, B.G. Nordestgaard.

Analysis and interpretation of the data: A.A. Sethi, A. Tybjærg-Hansen, B.G. Nordestgaard.

Drafting of the article: A.A. Sethi.

Critical revision of the article for important intellectual content: A. Tybjærg-Hansen, B.G. Nordestgaard.

Final approval of the article: A.A. Sethi, A. Tybjærg-Hansen, M.L.M. Grønholdt, Rolf Steffensen, P. Schnohr, B.G. Nordestgaard.

Provision of study materials or patients: M.L.M. Grønholdt, R. Steffensen, P. Schnohr.

Statistical expertise: A. Tybjærg-Hansen, B.G. Nordestgaard.

Obtaining of funding: A.A. Sethi, A. Tybjærg-Hansen, B.G. Nordestgaard.

Collection and assembly of data: M.L.M. Grønholdt, R. Steffensen, P. Schnohr.

Related articles in Annals:

Summaries for Patients
Mutations of the Angiotensinogen Gene and the Risk for Heart Disease and Stroke

Annals 2001 134: S5. [Full Text]  

This article has been cited by other articles:

				M.-Q. Xu, Z. Ye, F. B. Hu, and L. He Quantitative Assessment of the Effect of Angiotensinogen Gene Polymorphisms on the Risk of Coronary Heart Disease Circulation, September 18, 2007; 116(12): 1356 - 1366. [Abstract] [Full Text] [PDF]

				K. D. Marciante, J. C. Bis, M. J. Rieder, A. P. Reiner, T. Lumley, S. A. Monks, C. Kooperberg, C. Carlson, S. R. Heckbert, and B. M. Psaty Renin-Angiotensin System Haplotypes and the Risk of Myocardial Infarction and Stroke in Pharmacologically Treated Hypertensive Patients Am. J. Epidemiol., July 1, 2007; 166(1): 19 - 27. [Abstract] [Full Text] [PDF]

				A. P. Pilbrow, B. R. Palmer, C. M. Frampton, T. G. Yandle, R. W. Troughton, E. Campbell, L. Skelton, J. G. Lainchbury, A. M. Richards, and V. A. Cameron Angiotensinogen M235T and T174M Gene Polymorphisms in Combination Doubles the Risk of Mortality in Heart Failure Hypertension, February 1, 2007; 49(2): 322 - 327. [Abstract] [Full Text] [PDF]

				I. Goldenberg, A. J. Moss, D. Ryan, S. McNitt, S. W. Eberly, and W. Zareba Polymorphism in the Angiotensinogen Gene, Hypertension, and Ethnic Differences in the Risk of Recurrent Coronary Events Hypertension, October 1, 2006; 48(4): 693 - 699. [Abstract] [Full Text] [PDF]

				J. Frederiksen, K. Juul, P. Grande, G. B. Jensen, T. V. Schroeder, A. Tybjaerg-Hansen, and B. G. Nordestgaard Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study Blood, November 15, 2004; 104(10): 3046 - 3051. [Abstract] [Full Text] [PDF]

				A. A. Sethi, A. Tybjaerg-Hansen, R. V. Andersen, and B. G. Nordestgaard Nanogen Microelectronic Chip for Large-Scale Genotyping Clin. Chem., February 1, 2004; 50(2): 443 - 446. [Full Text] [PDF]

				K. Juul, A. Tybjaerg-Hansen, S. Marklund, N. H.H. Heegaard, R. Steffensen, H. Sillesen, G. Jensen, and B. G. Nordestgaard Genetically Reduced Antioxidative Protection and Increased Ischemic Heart Disease Risk: The Copenhagen City Heart Study Circulation, January 6, 2004; 109(1): 59 - 65. [Abstract] [Full Text] [PDF]

				P. Jacobsen, L. Tarnow, B. Carstensen, P. Hovind, O. Poirier, and H.-H. Parving Genetic Variation in the Renin-Angiotensin System and Progression of Diabetic Nephropathy J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2843 - 2850. [Abstract] [Full Text] [PDF]

				S. E. Bojesen, K. Juul, P. Schnohr, A. Tybjaerg-Hansen, and B.o. G. Nordestgaard Platelet glycoprotein IIb/IIIa PlA2/PlA2 homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men: The Copenhagen City Heart Study J. Am. Coll. Cardiol., August 20, 2003; 42(4): 661 - 667. [Abstract] [Full Text] [PDF]

				A. A. Sethi, B. G. Nordestgaard, and A. Tybjaerg-Hansen Angiotensinogen Gene Polymorphism, Plasma Angiotensinogen, and Risk of Hypertension and Ischemic Heart Disease: A Meta-Analysis Arterioscler. Thromb. Vasc. Biol., July 1, 2003; 23(7): 1269 - 1275. [Abstract] [Full Text] [PDF]

				A. A. Sethi, B. G. Nordestgaard, M.-L. M. Gronholdt, R. Steffensen, G. Jensen, and A. Tybjaerg-Hansen Angiotensinogen Single Nucleotide Polymorphisms, Elevated Blood Pressure, and Risk of Cardiovascular Disease Hypertension, June 1, 2003; 41(6): 1202 - 1211. [Abstract] [Full Text] [PDF]

				S.C. Kofoed, H.H. Wittrup, H. Sillesen, and B.G. Nordestgaard Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: The Copenhagen City Heart Study Eur. Heart J., March 2, 2003; 24(6): 567 - 576. [Abstract] [Full Text] [PDF]

				M. Dahl, A. Tybjaerg-Hansen, H. Sillesen, G. Jensen, R. Steffensen, and B. G. Nordestgaard Blood Pressure, Risk of Ischemic Cerebrovascular and Ischemic Heart Disease, and Longevity in {alpha}1-Antitrypsin Deficiency: The Copenhagen City Heart Study Circulation, February 11, 2003; 107(5): 747 - 752. [Abstract] [Full Text] [PDF]

				J. F. Meschia Addressing the Heterogeneity of the Ischemic Stroke Phenotype in Human Genetics Research Stroke, December 1, 2002; 33(12): 2770 - 2774. [Abstract] [Full Text] [PDF]

				P. B. Gorelick Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy: An Invited Review Stroke, March 1, 2002; 33(3): 862 - 875. [Abstract] [Full Text] [PDF]