Thromb Haemost 2000; 83(06): 803-806
DOI: 10.1055/s-0037-1613923
Commentary
Schattauer GmbH

The Rsal Polymorphism in the α-Fibrinogen Gene and Response of Plasma Fibrinogen to Physical Training

A Controlled Randomised Clinical Trial in Men
Rainer Rauramaa
1   From the Kuopio Research Institute of Exercise Medicine and Department of Physiology, University of Kuopio, Kuopio
2   Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio
,
Sari B. Väisänen
1   From the Kuopio Research Institute of Exercise Medicine and Department of Physiology, University of Kuopio, Kuopio
3   Department of Clinical Chemistry, Kuopio University Hospital, Kuopio, Finland
,
Raimo Kuhanen
1   From the Kuopio Research Institute of Exercise Medicine and Department of Physiology, University of Kuopio, Kuopio
,
Ilkka Penttilä
1   From the Kuopio Research Institute of Exercise Medicine and Department of Physiology, University of Kuopio, Kuopio
3   Department of Clinical Chemistry, Kuopio University Hospital, Kuopio, Finland
,
Claude Bouchard
4   Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, USA
› Author Affiliations
Further Information

Publication History

Received 19 August 1999

Accepted after resubmission 02 February 2000

Publication Date:
14 December 2017 (online)

Summary

We have previously reported cross-sectional data on an interaction effect between physical activity and α-fibrinogen Rsal polymorphism on fibrinogen in postmenopausal women. In the present controlled randomised study, we investigated the role of the Rsal polymorphism in determining the response of fibrinogen to long-term regular exercise. Middle-aged men (n = 140), randomly selected from the population registry, were randomised into an exercise or a reference group for a 3-year low intensity exercise intervention. Complete data were available in 125 men. The Rsal restriction enzyme detects threonine (Thr) to alanine change in the fibrinogen α codon 312. Anaerobic ventilatory threshold increased by 4%, but decreased by 2% in the exercise and reference groups, respectively. Mean fibrinogen did not decrease in either study group. However, in the exercise group, individual changes in anaerobic threshold explained 48% of the variance in fibrinogen changes in the Thr homozygotes. Our data offer a new aspect of beneficial effects of regular physical exercise on risk factors for coronary heart disease.

 
  • References

  • 1 Benderly M, Graff E, Reicher-Reiss H, Behar S, Brunner D, Goldbourt U. Fibrinogen is a predictor of mortality in coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study Group. Arterioscler Thromb Vasc Biol 1996; 16: 351-6.
  • 2 Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5.
  • 3 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WR, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 02: 533-7.
  • 4 Heinrich J, Balleisen L, Schulte H, Assmann G, van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men. Arterioscler Thromb 1994; 14: 54-9.
  • 5 Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332: 635-41.
  • 6 Ernst E, Resch KL. Therapeutic interventions to lower plasma fibrinogen concentration. Eur Heart J 1995; 16 (Suppl A): 47-53.
  • 7 Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991; 91: 191-205.
  • 8 Connelly JB, Cooper JA, Meade TW. Strenuous exercise, plasma fibrinogen, and factor VII activity. Br Heart J 1992; 67: 351-4.
  • 9 Rankinen T, Rauramaa R, Väisänen S, Penttilä I, Saarikoski S, Tuomilehto J, Nissinen A. Inverse relationship between physical activity and plasma fibrinogen in postmenopausal women. Atherosclerosis 1993; 102: 181-6.
  • 10 Rankinen T, Rauramaa R, Väisänen S, Penttilä IM, Uusitupa M. Relation of habitual diet and cardiorespiratory fitness to blood coagulation and fibrinolytic factors. Thromb Haemost 1994; 71: 180-3.
  • 11 Väisänen S, Rauramaa R, Penttilä I, Rankinen T, Gagnon J, Pérusse L, Chagnon M, Bouchard C. Variation in plasma fibrinogen over one year: relationships with genetic polymorphisms and non-genetic factors. Thromb Haemost 1997; 77: 884-9.
  • 12 Stratton JR, Chandler WL, Schwartz RS, Cerqueira MD, Levy WC, Kahn SE, Larson VG, Cain KC, Beard JC, Abrass IB. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. Circulation 1991; 83: 1692-7.
  • 13 Vanninen E, Laitinen J, Uusitupa M. Physical activity and fibrinogen concentration in newly diagnosed NIDDM. Diabetes Care 1994; 17: 1031-8.
  • 14 Montgomery HE, Clarkson P, Nwose OM, Mikailidis DP, Jagroop IA, Dollery C, Moult J, Benhizia F, Deanfield J, Jubb M, World M, McEwan JR, Winder A, Humphries S. The acute rise in plasma fibrinogen concentration with exercise is influenced by the G-453-A polymorphism of the beta-fibrinogen gene. Arterioscler Thromb Vasc Biol 1996; 16: 386-91.
  • 15 Schuit AJ, Schouten EG, Kluft C, de Maat M, Menheere PP, Kok FJ. Effect of strenuous exercise on fibrinogen and fibrinolysis in healthy elderly men and women. Thromb Haemost 1997; 78: 845-51.
  • 16 Kant JA, Fornace AJ, Saxe D, Simon MI, McBride OW, Crabtree GR. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. Proc Natl Acad Sci USA 1985; 82: 2344-8.
  • 17 Baumann RE, Henschen AH. Human fibrinogen polymorphic site analysis by restriction endonuclease digestion and allele-specific polymerase chain reaction amplification: identification of polymorphisms at positions A alpha 312 and B beta 448. Blood 1993; 82: 2117-24.
  • 18 Rauramaa R, Väisänen S, Nissinen A, Rankinen T, Penttilä I, Saarikoski S, Tuomilehto J, Gagnon J, Pérusse L, Bouchard C. Physical activity, fibrinogen plasma level and gene polymorphisms in postmenopausal women. Thromb Haemost 1997; 78: 840-4.
  • 19 Lee DH, Hong SH, Song J, Min WK, Kim JQ. Fibrinogen gene polymorphism in a non-Caucasian population. Clin Biochem 1999; 32: 113-7.
  • 20 Rauramaa R, Rankinen T, Tuomainen P, Väisänen S, Mercuri M. Inverse relationship between cardiorespiratory fitness and carotid atherosclerosis. Atherosclerosis 1995; 112: 213-21.
  • 21 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haemat 1957; 17: 237-46.
  • 22 Baumann RE, Henschen AH. Linkage disequilibrium relationships among four polymorphisms within the human fibrinogen gene cluster. Hum Genet 1994; 94: 165-70.
  • 23 Rankinen T, Rauramaa R, Väisänen S, Halonen P, Penttilä I. Blood coagulation and fibrinolytic factors are unchanged by aerobic exercise or fat modified diet. Fibrinolysis 1994; 08: 48-53.
  • 24 Humphries SE, Cook M, Dubowitz M, Stirling Y, Meade TW. Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations. Lancet 1987; 01: 1452-5.
  • 25 Collen D, Semeraro N, Tricot JP, Vermylen J. Turnover of fibrinogen, plasminogen, and prothrombin during exercise in man. J Appl Physiol 1977; 42: 865-73.
  • 26 Rosenson RS, Tangney CC, Hafner JM. Intraindividual variability of fibrinogen levels and cardiovascular risk profile. Arterioscler Thromb 1994; 14: 1928-32.