The Effect of Factor XIII V34L Polymorphism in Obstructive Sleep Apnea Patients

Abstract

Aim: In the Obstructive Sleep Apnea Syndrome (OSAS), the organism is exposed to hypoxic effects. Chronic hypoxia has thrombotic, vasoactive and inflammatory effects on cardiovascular system. This triggers the processes progressing to cardiovascular disease. While the pathological effects to which the patients are exposed are the same, marked differences are observed between patients in the progression of OSAS. Individual protective factors are thought to be effective in the development of these differences. In some studies, it was reported that the Val34Leu polymorphism of Factor XIII, which is also known as fibrin-stabilizing factor, might have a protective effect against cardiovascular diseases. In the light of these studies, we aimed to investigate whether this polymorphism has any effects on the development of the differences in the progression of the OSAS patients. Materials and Methods: The patient group was selected from patients admitted to the our Sleep Laboratory. Total 119 of subjects, 44 OSAS patients, 32 OSAS patients with cardio vascular diseases (CVD) and 43 controls were enrolled in the study. The control group consisted of healthy volunteers who had no symptoms of OSAS and scored 0 on the Epworth sleepiness scale. In order to determine gene mutations, DNA isolation was performed from peripheral blood samples. Data were analyzed by SPSS 15.0 package program. Results: While mean weight and BMI were significantly different, no significant differences were found between patient and control groups in terms of FXIII Val34Leu allele distributions. Key words: Obstructive Sleep Apnea, Polymorphism, Mutation

Keywords

• Obstructive Sleep Apnea, Polymorphism, Mutation

Obstrüktif Uyku Apneli Hastalarda Faktör XIII V34L Polimorfizminin Etkisi

Öz

Amaç: Obstrüktif uyku apne sendromunda (OUAS) organizma hipoksik etkilere maruz kalmaktadır. Kronik hipoksi kardiyovasküler sistem üzerinde trombotik, vazoaktif ve inflamatuvar etkilere sahiptir. Bu da kardiyovasküler hastalık geşimine yol açansüreçleritetiklemektedir. Aynı patolojik etkilere maruz kalmalarına rağmen OUAS'nun progresyonunda hastalar arasında belirgin farklar gözlemlenmektedir. Bireysel koruyucu faktörlerin bu farklılıkların oluşmasında etkili olduğu sanılmaktadır. Bazı çalışmalarda fibrin stabilize edici faktör olarak ta bilinen faktör XIII'ün Val34Leu polimorfizminin kardiyovasküler hastalıklara karşı koruyucu bir etki gösterdiği rapor edilmiştir. Bu çalışmalar ışığında bu polimorfizmin OUAS hastalarının progresyonundaki farklılıkların oluşmasında herhangi bir etkiye sahip olup olmadığını araştırmayı amaçladık. Materyal ve Metod: Hasta grubunu uyku laboratuvarımıza başvuran hastalardan seçtik. 44 normal OUAS hastası, 32 kardiyovasküler hastalıklı (KVH) OUAS hastası ve 43 kontrol grubu olmak üzere toplam 119 kişi çalışmamıza dahil edildi. Kontrol grubu OUAS semptomları göstermeyen Epworth uykusuzluk skala değeri 0 olan sağlıklı gönüllülerden oluşturuldu. Gen mutasyonlarını belirlemek için periferik kan örneklerinden DNA izolasyonu yapıldı. Veriler SPSS 15.0 istatistik programı kullanılarak analiz edildi. Sonuçlar: Hasta ve kontrol grupları arasında kilo ve BMI açısından önemli farklar bulunurken FXIII Val34Leu allel dağılımları açısından önemli bir farklılık bulunamamıştır. Anahtar kelimeler: Obstrüktif Uyku Apne, Polimorfizm, Mutasyon

Anahtar Kelimeler

• Obstrüktif Uyku Apne, Polimorfizm, Mutasyon

References

1. Young T, Palta M, Dempsey J, et al. The occurrence of sleep disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230–5.
2. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med 2005; 142: 187–97.
3. Edwards N, Wilcox I, Sullivan CE. Sleep apnoea in women. Thorax 1998; 53 Suppl 3:12–5.
4. Grote L, Hedner J, Peter JH. Sleep-related breathing disorder is an independent factor for uncontrolled hypertension. J Hypertens 2000; 18: 679–85.
5. Shahar E, Whitney CW, Redline S, et al. Sleep-disordered breathing and cardiovascular disease cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001; 163: 19–25.
6. Banno K, Shiomi T, Sasanabe R, et al. Sleep-disordered breathing in patients with idiopathic cardiomyopathy. Circ J 2004; 68 (4): 338–42.
7. Mooe T, Franklin KA, Wiklund U, et al. Sleep-disordered breathing and myocardial ischemia in patients with coronary artery disease. Chest 2000; 117: 1597–602.
8. Robinson GV, Pepperell JC, Segal HC, et al. Circulating cardiovascular risk factors in obstructive sleep apnea: data from randomised controlled trials. Thorax 2004; 59: 777– 82.

9. Zamarro´n C, Ricoy J, Riveiro A, et al. Plasminogen activator inhibitor-1 in obstructive sleep apnea patients with and without hypertension. Lung 2008; 186: 151–6.
10. Partinen M, Jamieson A, Guilleminault C. Long-term outcome for obstructive sleep apnea syndrome patients. Chest 1988; 94: 1200-4.
11. Siebenlist KR, Meh DA, Mosesson MW. Plasma factor XIII binds specifically to fibrinogen molecules containing chains. Biochemistry 1996;35: 10448-53.
12. Ichinose A. Physiopathology and regulation of factor XIII. Thromb Haemost 2001; 86: 57-65.
13. Bereczky Z, Katona E, Muszbek L. Fibrin stabilization (factor XIII), fibrin structure and thrombosis. Pathophysiol Haemost Thromb 2004; 33: 430–7.
14. Wells P, Anderson J, Scarvelis D, et al. Factor XIII Val34Leu variant is protective against venous thromboembolism: a huge review and meta-analysis. Am J Epidemiol 2006; 164: 101–9.
15. Anwar R, Gallivan L, Edmonds SD, et al. Genotype/phenotype correlations for coagulation Factor XIII: specific normal polymorphisms are associated with high or low Factor XIII specific activity. Blood 1999; 93: 897–905.
16. Balogh I, Szôke G, Kárpáti L, et al. Val34Leu polymorphism of plasma FXIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000; 96: 2479-86.
17. Kohler HP, Futers TS, Grant PJ. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease. Thromb Haemost 1999; 81: 511-5.
18. Catto AJ, Kohler HP, Coore J, et al. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood 1999; 93: 906-8.
19. QIAamp DNA Mini Kit and QIAamp DNA Blood Mini Kit Handbook, http://www.qiagen.com/literature/handbooks.
20. Grundmann U, Aman E, Zettlmeissl G, et al. Characterization of a cDNA coding for human factor XIIIa. Proc Natl Acad Sci USA 1986; 83: 8024-8.
21. Corral J, Iniesta JA, González-Conejero , et al. Detection of factor V Leiden from a drop of blood by PCR-SSCP. Thromb Haemost 1996; 76: 735-7.
22. Kato M, Roberts-Thomson P, Phillips BG, et al. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 2000; 102:2607- 10.
23. Schulz R, Mahmoudi S, Hattar K, et al. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea: impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 2000; 162: 566-70.
24. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997; 82: 1313-6.
25. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated C- reactive protein in patients with obstructive sleep apnea. Circulation 2002; 105:2462-4.
26. Sanner BM, Konermann M, TepelM, et al. Platelet function in patients with obstructive sleep apnoea syndrome. Eur Respir J 2000; 16: 648-52.
27. Bokinsky G, Miller M, Ault K, et al. Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure: a preliminary investigation. Chest 1995; 108: 625-30.
28. Chin K, Kita H, Noguchi T, et al. Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnea syndrome. QJM 1998; 91: 627-6.
29. Flint J, Harding RM, Boyce AJ, et al. The population genetics of the haemoglobinopathies. In: Higgs DR, Weatherall DJ (eds). Baillie`re’s Clinical Haematology; ‘Haemoglobinopathies’. Baillie`re Tindall and W.B. Saunders: London, 1998; 1–51.
30. Daniel Z, Lachgar A, Chams V, et al. C-C chemokines, pivotal in protection against HIV type 1 infection, Proc Nat Acad Sci USA 1998: 95 (7):3857–61.
31. Balogh I, Szôke G, Kárpáti L, Wartiovaara U, Katona É, Komáromi I, Haramura G, Pfliegler G, Mikkola H, Muszbek L. Val34Leu polymorphism of plasma FXIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000; 96: 2479-86.
32. Kohler HP, Stickland MH, Ossei-Gerning N, et al. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998; 79: 8 -13.
33. Wartiovaara U, Perola M, Mikkola H, et al. Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finnish males. Atherosclerosis 1999; 142: 295-300.
34. Kakko S, Elo T, Tapanainen JM, et al. Polymorphisms of genes affecting thrombosis and risk of myocardial infarction. Eur J Clin Invest 2002; 32: 643-8.
35. Franco RF, Pazin-Filho A, Tavella AH, et al. Factor XIII Val34Leu and the risk of myocardial infarction. Haematologica 2000; 85: 67-71.
36. Gemmati D, Serino ML, Ongaro A, et al. A common mutation in the gene for coagulation factor XIII-A (Val34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases. Am J Hematol 2001; 67: 183-8.
37. Renner W, Köppel H, Hoffmann C. Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria. Thromb Res 2000; 99: 35-9.
38. Elbaz A, Poirier O, Canaple S, et al. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood 2000; 95: 586-91.