Skip to main content
PMC home page
Heart logoLink to Heart
. 2000 Nov;84(5):548–552. doi: 10.1136/heart.84.5.548

Polymorphisms of the P-selectin gene and risk of myocardial infarction in men and women in the ECTIM extension study

F Kee 1, C Morrison 1, A Evans 1, E McCrum 1, D McMaster 1, J Dallongeville 1, V Nicaud 1, O Poirier 1, F Cambien 1, G BAXTER 1
PMCID: PMC1729474  PMID: 11040019

Abstract

BACKGROUND AND OBJECTIVE—Studies in animal models and humans implicate cell adhesion molecules in atherogenesis but their role in mediating the risk of myocardial infarction is unclear. The ECTIM (étude cas-temoin de l'infarctus myocarde) extension study was established to determine whether a previously implicated polymorphism of the P-selectin gene was associated with myocardial infarction risk in men and women in Belfast and Glasgow.
PATIENTS AND STUDY SETTING—696 cases with a recent myocardial infarction and 561 age matched controls (both male and female) were recruited into a case-control study in MONICA project areas of Belfast and Glasgow.
METHODS—Demographic and lifestyle information was collected by interview administered questionnaire, and each subject was examined and provided a blood sample for DNA extraction. The polymerase chain reaction (PCR) was used to amplify regions encompassing the P-selectin Thr→Pro (A/C) polymorphism at position 715. Genotype odds ratios for myocardial infarction were estimated by logistic regression adjusted for population, age, and sex.
RESULTS—There was no significant association between conventional risk factors (such as hypercholesterolaemia, increased body mass index, or raised blood pressure) and either the rare or the common Pro715 allele of the P-selectin gene in controls. Overall, comparing Pro715/Pro715 and Pro715/Thr715 with Thr715/Thr715, with adjustment for centre, age, and sex, the odds ratio was 0.78 (95% confidence interval 0.60 to 1.00) (p = 0.054), indicating a "protective" effect of the less common Pro715 allele. There was no significant heterogeneity in odds ratios between men and women either in this sample or when combined with the original ECTIM subjects.
CONCLUSIONS—In a large population based study in two regions of the UK, we have been able to corroborate the earlier ECTIM findings of a lower frequency of the Thr/Pro715 polymorphism in subjects with myocardial infarction. An apparently "protective effect" of similar magnitude also seems to apply to women.


Keywords: P-selectin; cell adhesion molecules; atherogenesis

Full Text

The Full Text of this article is available as a PDF (127.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alaupovic P., Lee D. M., McConathy W. J. Studies on the composition and structure of plasma lipoproteins. Distribution of lipoprotein families in major density classes of normal human plasma lipoproteins. Biochim Biophys Acta. 1972 Apr 18;260(4):689–707. [PubMed] [Google Scholar]
  2. Blann A. D., Faragher E. B., McCollum C. N. Increased soluble P-selectin following myocardial infarction: a new marker for the progression of atherosclerosis. Blood Coagul Fibrinolysis. 1997 Oct;8(7):383–390. [PubMed] [Google Scholar]
  3. Dong Z. M., Chapman S. M., Brown A. A., Frenette P. S., Hynes R. O., Wagner D. D. The combined role of P- and E-selectins in atherosclerosis. J Clin Invest. 1998 Jul 1;102(1):145–152. doi: 10.1172/JCI3001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Evans A. E., Patterson C. C., Mathewson Z., McCrum E. E., McIlmoyle E. L. Incidence, delay and survival in the Belfast MONICA Project coronary event register. Rev Epidemiol Sante Publique. 1990;38(5-6):419–427. [PubMed] [Google Scholar]
  5. Herrmann S. M., Ricard S., Nicaud V., Mallet C., Evans A., Ruidavets J. B., Arveiler D., Luc G., Cambien F. The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction. Hum Mol Genet. 1998 Aug;7(8):1277–1284. doi: 10.1093/hmg/7.8.1277. [DOI] [PubMed] [Google Scholar]
  6. Ishiwata S., Tukada T., Nakanishi S., Nishiyama S., Seki A. Postangioplasty restenosis: platelet activation and the coagulation-fibrinolysis system as possible factors in the pathogenesis of restenosis. Am Heart J. 1997 Apr;133(4):387–392. doi: 10.1016/s0002-8703(97)70178-9. [DOI] [PubMed] [Google Scholar]
  7. Kaikita K., Ogawa H., Yasue H., Sakamoto T., Suefuji H., Sumida H., Okumura K. Soluble P-selectin is released into the coronary circulation after coronary spasm. Circulation. 1995 Oct 1;92(7):1726–1730. doi: 10.1161/01.cir.92.7.1726. [DOI] [PubMed] [Google Scholar]
  8. Kumar A., Hoover J. L., Simmons C. A., Lindner V., Shebuski R. J. Remodeling and neointimal formation in the carotid artery of normal and P-selectin-deficient mice. Circulation. 1997 Dec 16;96(12):4333–4342. doi: 10.1161/01.cir.96.12.4333. [DOI] [PubMed] [Google Scholar]
  9. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Peter K., Nawroth P., Conradt C., Nordt T., Weiss T., Boehme M., Wunsch A., Allenberg J., Kübler W., Bode C. Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. Arterioscler Thromb Vasc Biol. 1997 Mar;17(3):505–512. doi: 10.1161/01.atv.17.3.505. [DOI] [PubMed] [Google Scholar]
  11. Wenzel K., Ernst M., Rohde K., Baumann G., Speer A. DNA polymorphisms in adhesion molecule genes--a new risk factor for early atherosclerosis. Hum Genet. 1996 Jan;97(1):15–20. doi: 10.1007/BF00218826. [DOI] [PubMed] [Google Scholar]

Articles from Heart are provided here courtesy of BMJ Publishing Group

RESOURCES