nach oben

Journal of Thrombosis and Thrombolysis

Erschienen in:

01.12.2006

A comprehensive analysis of 12 thrombophilic mutations and related parameters in patients with inflammatory bowel disease: data from Turkey

verfasst von: Şerif Yılmaz, Kadim Bayan, Yekta Tüzün, Sabri Batun, Abdullah Altıntaş

Erschienen in: Journal of Thrombosis and Thrombolysis | Ausgabe 3/2006

Einloggen, um Zugang zu erhalten

Abstract

Background

Possible association of inflammatory bowel disease (IBD) with the most common inherited prothrombotic conditions has been the focus of many investigations. Advance in modern molecular biology is expanding the thrombophilia evaluation steadily. We tried to put forward a comprehensive thrombophilic profile in IBD and to see the probable role of this profile in pathogenesis.

Methods

A total of 60 adults (33 patients and 27 healthy controls) were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen-455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. Besides, we evaluated many related blood parameters such as protein C, protein S, AT-III, IL-6, TNF-alpha, Apo-A1, Apo-B100, homocysteine (tHcy) etc. using commercially available assays.

Results

The frequencies of genetic polymorphisms were found to be statistically insignificant among patients and controls, except for three: Beta-Fibrinogen-455G-A, MTHFR A1298C and ACE-I/D. Two patients with a history of deep venous thrombosis had more than one polymorphism. Patients with MTHFR C677T and MTHFR A1298C gene mutations had a similar mean tHcy levels with controls. Patients with Apolipoprotein B R3500Q and Apolipoprotein E4 gene mutations had similar mean LDL-cholesterol levels. Mean total cholesterol and triglyceride levels were similar in patients and controls of Apo E2, E3, E4 alleles.

Conclusion

Predominantly, the presence of genetic mutations that predispose to hypercoagulable states does not appear to be in correlation with IBD. There was a statistical difference between the proportions of the mutated allele frequencies of Beta-Fibrinogen-455G-A, MTHFR A1298C and ACE-I/D in IBD.

Bernstein CN, Blanchard JF, Houston D et al (2001) The incidence of venous thromboembolic disease among patients with IBD: a population-based study. Thromb Haemost 85:430–434PubMed

Talbot RW, Heppell J, Dozois RR et al (1986) Vascular complications of inflammatory bowel disease. Mayo Clin Proc 61:140–145PubMed

Dhillon AP, Anthony A, Sim R et al (1992) Mucosal capillary thrombi in rectal biopsies. Histopathology 21:127–133PubMed

Wakefield AJ, Sawyer AM, Hudson M et al (1991) Smoking, the oral contraceptive pill and Crohn’s disease. Dig Dis Sci 36:1147–1150CrossRefPubMed

Logan RFA, Kay CR (1989) Oral contraception, smoking and inflammatory bowel disease findings in the Royal College of General Practitioners oral contraceptive study. Int J Epidemiol 18:105–107PubMed

Thompson N, Wakefield AJ, Pounder RE (1995) Inherited disorders of coagulation appear to protect against inflammatory bowel disease. Gastroenterology 108:1011–1015CrossRefPubMed

Crowther MA, Kelton JG (2003) Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med 138(2):128–134PubMed

Martinelli I (2001) Risk factors in venous thromboembolism. Thromb Haemost 86(1):395–403PubMed

Harvey R, Bradshaw J (1980) A simple index of Crohn’s disease activity. Lancet 1:514CrossRefPubMed

10.

Truelove S, Witts L (1955) Cortisone in ulcerative colitis. Br Med J 2:1041–1048

11.

Kirsner JB, Spencer JA (1963) Family occurrences of ulcerative colitis, regional enteritis, and ileocolitis. Ann Intern Med 59:133–144PubMed

12.

Papa A, Danese S, Grillo A et al (2003) Review article: inherited thrombophilia in inflammatory bowel disease. Am J Gastroenterol 98(6):1247–1251CrossRefPubMed

13.

Wakefield AJ, Sawyerr AM, Dhillon AP et al (1989) Pathogenesis of Crohn’s disease: multifocal gastrointestinal infarction. Lancet 2(8671):1057–1062CrossRefPubMed

14.

Jackson LM, O’Gorman PJ, O’Connell J et al (1997) Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden. QJM 90(3):183–188CrossRefPubMed

15.

Donmez Y, Kanadasi M, Tanriverdi K et al (2004) Prothrombin 20210GA and factor V Leiden mutations in patients less than 55 years old with myocardial infarction. Jpn Heart J 45(3):505–512CrossRefPubMed

16.

Castoldi E, Rosing J. Factor V (2004) Leiden: a disorder of factor V anticoagulant function. Curr Opin Hematol 11(3):176–181CrossRefPubMed

17.

Bloemenkamp KW, Rosendaal FR, Helmerhorst FM et al (1995) Enhancement by factor V Leiden mutation of risk of deep vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 346:1593–1596CrossRefPubMed

18.

Rosendaal FR, Koster T, Vandenbroucke JP et al (1995) High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 86:4700–4702

19.

Haslam N, Standen GR, Probert GS (1999) An investigation of the association of the factor V Leiden mutation and inflammatory bowel disease. Eur J Gastroenterol Hepatol 11:1289–1291CrossRefPubMed

20.

Over HH, Ulgen S, Tuglular T et al (1998) Thrombophilia and inflammatory bowel disease: Does factor V mutation have a role? Eur J Gastroenterol Hepatol 10:827–829PubMedCrossRef

21.

Haslam N, Standen GR, Probert CS (2001) An investigation of the association of the prothrombin G20210A gene mutation and inflammatory bowel disease: Factor II and IBD. Inflamm Bowel Dis 7:133–135CrossRefPubMed

22.

Papa A, Stefano V, Gasbarrini A et al (2000) Prevalence of factor V Leiden and the G20210A prothrombin-gene mutation in inflammatory bowel disease. Blood Coagul Fibrinolysis 11:499–503CrossRefPubMed

23.

Bernardi F, Faioni EM, Castoldi E et al (1997) A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood 90:1552–1557PubMed

24.

Mikkola H, Syrjala M, Rasi V et al (1994) Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood 84(2):517–525PubMed

25.

Saibeni S, Vecchi M, Faioni EM et al (2003) Val34Leu factor XIII polymorphism in Italian patients with inflammatory bowel disease. Dig Liver Dis 35(1):32–36CrossRefPubMed

26.

Dong QL, Zhang C (2004) Association between the polymorphism of beta-fibrinogen gene-455G/A and ischemic stroke. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 21(3):274–276PubMed

27.

Humphries S, Henry J, Montgomery H (1999) Gene–environment interaction in the determination of levels of haemostatic variables involved in thrombosis and fibrinolysis. Blood Coagul Fibrinolysis 10:S17–S21PubMed

28.

Eriksson P, Kallin B, Van’t Hooft FM et al (1995) Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 92:1851–1855CrossRefPubMed

29.

Tassies D, Espinosa G, Munoz-Rodriguez FJ et al (2000) The 4G/5G polymorphism of the type 1 plasminogen activator inhibitor gene and thrombosis in patients with antiphospholipid syndrome. Arthritis Rheum 43: 2349–2358CrossRefPubMed

30.

Stegnar M, Uhrin P, Peternel P et al (1998) The 4G/5G sequence polymorphism in the promoter of plasminogen activator inhibitor-1 (PAI-1) gene: relationship to plasma PAI-1 level in venous thromboembolism. Thromb Haemost 79: 975–979PubMed

31.

Dossenbach-Glaninger A, van Trotsenburg M, Dossenbach M et al (2003) Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin Chem 49(7):1081–1086CrossRefPubMed

32.

Segui R, Estelles A, Mira Y et al (2000) PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects. Br J Haematol 111(1):122–128CrossRefPubMed

33.

Hefler L, Jirecek S, Heim K et al (2004) Genetic polymorphisms associated with thrombophilia and vascular disease in women with unexplained late intrauterine fetal death: a multicenter study. J Soc Gynecol Investig 11(1):42–44CrossRefPubMed

34.

Sans M, Tassies D, Pellise M et al (2003) The 4G/4G genotype of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene is a determinant of penetrating behaviour in patients with Crohn’s disease. Aliment Pharmacol Ther 17(8):1039–1047CrossRefPubMed

35.

Slowik A, Dziedzic T, Turaj W et al (2004) A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke 35(7):1589–1593CrossRefPubMed

36.

den Heijer M, Koster T, Blom HJ et al (1996) Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 334:759–762CrossRef

37.

Morgenstern I, Raimakers MTM, Peters WHM et al (2003) Homocysteine, cysteine and glutathione in human colonic mucosa: elevated levels of homocysteine in patients with inflammatory bowel disease. Dig Dis Sci 48:2083–2090CrossRefPubMed

38.

van der Put NM, Gabreels F, Stevens EM et al (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neuraltube defects? Am J Hum Genet 62:1044–1051CrossRefPubMed

39.

Weisberg I, Tran P, Christensen B et al (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64:169–172CrossRefPubMed

40.

Hanson NQ, Aras O, Yang F et al (2001) C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease. Clin Chem 47(4):661–666PubMed

41.

Oldenburg B, Fijnheer R, van der Griend R et al (2000) Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications? Am J Gastroenterol 95(10):2825–2830CrossRefPubMed

42.

Brown NJ, Vaughan DE (2000) Prothrombotic effects of angiotensin. Adv Intern Med 45:419–429PubMed

43.

Rigat B, Hubert C, Alhenc-Gelas MF et al (1990) An insertion/deletion polymorphism in the angiotensin converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346PubMedCrossRef

44.

Butler R, Morris AD, Burchell B et al (1999) DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans. Hypertension 33:1164–1168PubMed

45.

Bedir A, Arik N, Adam B et al (1999) Angiotensin converting enzyme gene polymorphism and activity in Turkish patients with essential hypertension. Am J Hypertens 12:1038–1043CrossRefPubMed

46.

Brown MS, Goldsteın JL (1986) A receptor mediated pathway for cholesterol homeostasis. Science 232:34–47CrossRefPubMed

47.

Tybjaerg-Hansen A, Steffensen R, Meinertz H et al (1998) Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease. N Engl J Med 338:1577–1584CrossRefPubMed

48.

Miller J (1990) Dyslipoproteinaemia of liver disease. Bailliers Clin Endocrinol Metab 4:807–832CrossRef

49.

Belo L, Gaffney D, Caslake M et al (2004) Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies. Eur J Obstet Gynecol Reprod Biol 112(1):9–15CrossRefPubMed

50.

Scuteri A, Bos AJ, Zonderman AB et al (2001) Is the apoE4 allele an independent predictor of coronary events? Am J Med 110(1):28–32CrossRefPubMed

Titel: A comprehensive analysis of 12 thrombophilic mutations and related parameters in patients with inflammatory bowel disease: data from Turkey
verfasst von: Şerif Yılmaz
Kadim Bayan
Yekta Tüzün
Sabri Batun
Abdullah Altıntaş
Publikationsdatum: 01.12.2006
Verlag: Kluwer Academic Publishers-Plenum Publishers
Erschienen in: Journal of Thrombosis and Thrombolysis / Ausgabe 3/2006
Print ISSN: 0929-5305
Elektronische ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-006-9032-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2006

Evaluation of oxidative stress in the thrombolysis of pulmonary embolism

A “two-step” educational approach for patients taking oral anticoagulants does not improve therapy control

Osteoprotegerin is not associated with angiographic coronary calcification

Left main coronary thrombosis with essential thrombocythemia

Platelet count, mean platelet volume, platelet distribution width, and plateletcrit do not correlate with optical platelet aggegation responses in healthy volunteers

Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase