Association of the plasminogen activator inhibitor-1(PAI-1) gene 4G/5G promoter polymorphism in Buerger's disease (Tromboangiitis obliterans)

Sinasi Manduz, Nurkay Katrancioglu, Oguz Karahan, Oztürk Ozdemir

.

DOI: 10.4236/health.2010.25068                

Abstract

Thromboangiitis obliterans (TAO) is an unusual tobacco-associated vasculopathy that is a non- atherosclerotic inflammatory disorder of unkn- own etiology that affects small and medium- sized vessels of the extremities. The single guanosine nucleotide deletion/insertion polym- orphism (4G/5G) at -675 bp in promoter region of the PAI-1 gene is the major genetic determi- nant of PAI-1 expression. Plasma PAI-1 level is higher in people with the homozygous 4G genotype than in those with the 5G/5G genotype and renders higher transcription activity. The aim of this study was to determine the status and the role of PAI-1 gene 4G/5G promoter polymorphism in patients with Buerger's disease (Thromboangiitis obliterans—TAO). The current case-control study included 30 consecutive pat- ients with Buerger's disease (mean age 42.9 ± 14.3 years, 28 men and 2 women), and 30 healthy volunteers (mean age 40.9 ± 4.79 years, 27 men and 3 women) between January 2006 and September 2009. Patients and control cases were genotyped for the 4G/5G polymorphism using the multiplex PCR based stripassay reverse hybridisation technique. It was found that heterozygote PAI-1 gene polymorphisms (p < 0.05) was significantly more frequent in patients with TAO in the current results. There was a significant difference in genotype distribution between the two groups (P < 0.001). The 4G allele occurred more frequently in the patient group of heavy smokers (P = 0.05). The current study shows the higher prevalence of of 4G allele in TAO patients in Sivas population means gene may predispose to TAO.

Keywords

Thromboangiitis Obliterans; Genetic Polymorphisms; PAI-1

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Buerger, L. (1952) Thrombo-angiitis obliterans: A study of the vascular lesions leading to presenile spontaneous gangrene. American Journal of Medicine, 13(5), 526- 532.
[2]	Brodmann, M., Renner, W., Stark, G., Winkler, M., Pabst, E., Hofmann, C. and Pilger, E. (2000) Prothrombotic risk factors in patients with thrombangitis obliterans. Thrombosis Research, 99(5), 483-486.
[3]	Cooper, L.T., Tse, T.S., Mikhail, M.A., Mcbane, R.D., Stanson, A.W. and Ballman, K.V. (2004) Long-term survival and amputation risk in thromboangiitis obliterans (Buerger’s disease). Journal of the American College of Cardiology, 44(12), 2410-2411.
[4]	Taşoğlu, I., Hanedan, O. and Ulus, A.T. (2008) Thromboangiitis obliterans (buerger hastalığı). Turkiye Klinikleri Journal of General Surgery Special Topics, 1(3), 15- 25.
[5]	Szuba, A. and Cooke, J.P. (1998) Thromboangiitis obliterans. An update on Buerger’s disease. Western Journal of Medicine, 168(4), 255-260.
[6]	Özen, F., Manduz, Ş., Katrancıoğlu, N., Karahan, O., Köksal, B. and Özdemir, Ö. (2009) Tromboanjiitis obliterans hastalarında protrombotik gen polimorfizminin rolü turkiye klinikleri. Journal of Cardiovascular Science, 21(2), 160-164.
[7]	Isserhoff, R.R. and Rifkin, D.B. (1983) Plasminogen is present in the basal layer of the epidermis. Journal of Investigative Dermatology, 80, 297-299.
[8]	Herouy, Y., Trefzer, D., Hellstern, M.O., Stark, G.B., Vanscheıdt, W., Schoè, P.F.E. and Norgauer J. (2000) Plasminogen activation in venous leg ulcers. British Journal of Dermatology, 143(5), 930-936.
[9]	Isordia-Salas, I., Leaños-Miranda, A., Sainz, I.M., Reyes- Maldonado, E. and Borrayo-Sánchez, G. (2009) Association of the plasminogen activator inhibitor-1 gene 4G/5G polymorphism with ST elevation acute myocardial infarction in young patients. Revista Española de Cardiología, 62(4), 365-372.
[10]	Foley, S. and Gibbs, H. (2008) Muir painful digital infarction in a male smoker treated as Buerger’s disease. Australasian Journal of Dermatology, 49(2), 94-97.
[11]	Stammler, F., Diehm, C., Hsu, E., Stockinger, K. and Amendt, K. (1996) The prevalence of hyperhomocysteinemia in thrombangitis obliterans. Does homocsteine play a role pathogenetically? Deutsche medizinische Wochenschrift, 121(46), 1417-1423.
[12]	Chenl, Z., Takahashi, M., Naruse, T., Nakajima, T., Chen, Y.W., Inoue, Y., Ishikawa, I., Iwail, T. and Kimura, A. (2007) Synergistic contribution of CD14 and HLA loci in the susceptibility to Buerger disease. Human Genetics, 122(3-4), 367-372.
[13]	Yenicesu, G.I., Cetin, M., Ozdemir, O., Cetin, A., Ozen, F., Yenicesu, C., Yildiz, C. and Kocak, N. (2009) A prospective case-control study analyzes 12 thrombophilic gene mutations in turkish couples with recurrent pregnancy loss. American Journal of Reproductive Immuno- logy, 63(2), 126-136.
[14]	Abboud, N., Ghazouani, L., Saidi, S., Ben-Hadj-Khalifa, S., Addad, F., Almawi, W.Y. and Mahjoub, T. (2010) Association of PAI-1 4G/5G and -844G/A gene polymorphisms and changes in PAI-1/tissue plasminogen activator levels in myocardial infarction: A case-control study. Genetic Testing and Molecular Biomarkers, 14(1), 23- 27.
[15]	Francis, C.W. (2002) Plasminogen activator inhibitor-1 levels and polymorphisms. Archives of Pathology & Laboratory Medicine, 126(11), 1401-1404.
[16]	Akar, N., et al. (2000) Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in turkish deep vein thrombotic patients with and without FV1691 G-A. Thrombosis Research, 97, 227-230.
[17]	Choudhury, N.A., Pietraszek, M.H., Hachiya, T., Baba, S., Sakaguchi, S., Takada, Y. and Takada, A. (1992) Plasminogen activators and plasminogen activator inhibitor 1 before and after venous occlusion of the upper limb in thromboangiitis obliterans (Buerger’s disease). Thrombosis Research, 66(4), 321-329.
[18]	Eroglu, A., Ulu, A. and Akar, N. (2006) Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients with and without thrombosis. Journal of Thrombosis and Thrombolysis, 22(2), 111-112.
[19]	Boekholdt, S.M., Bijsterveld, N.R., Moons, A.H., Levi, M., Büller, H.R. and Peters, R.J. (2001) Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: A systematic review. Circulation, 104(25), 3063-3068.
[20]	Ye, Z., Liu, E.H., Higgins, J.P., Keavney, B.D., Lowe, G.D., Collins, R. and Danesh J. (2006) Seven haemostatic gene polymorphisms in coronary disease: Meta-analysis of 66, 155 cases and 91,307 controls. Lancet, 367(9511), 651- 658.
[21]	Tsantes, A.E., Nikolopoulos, G.K., Bagos, P.G., Rapti, E., Mantzios, G., Kapsimali, V. and Travlou, A. (2007) Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis. A meta-analysis. Journal of Thrombosis and Haemostasis, 97(6), 907-913.