Matrix Metalloproteinase-9 Level and Gene Polymorphism in Sleep Disordered Breathing Patients with or without Cardiovascular Disorders

Year 2013, , 8 - 12, 01.01.2013

Meral Yüksel Hacer Kuzu Okur Ayliz Velioğlu Öğünç Zerrin Pelin

https://doi.org/10.5152/balkanmedj.2012.068

Abstract

Objective: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the matrix metalloproteinase-9 (MMP-9) level and MMP-9 gene polymorphism in sleep apnea patients with or without cardiovascular disease. Study Design: Case-control study. Material and Methods: Two hundred nine patients [Mean age (±SD), 47 (±12) yrs; M/F, 170/39] diagnosed with sleep-disordered breathing were included in the study. Serum MMP-9 level was performed using enzyme-linked immunosorbant assay (ELISA) and MMP-9 gene polymorphism with polymerase chain reaction-restriction fragment length polymorphism. We divided the patient group into two subgroups: (1) patients with confirmed cardiovascular disease, i.e. CV-P Group and (2) patients without cardiovascular disease, CV-N Group. We compared all parameters between the two groups. Results: There were 56 OSAS patients with cardiovascular disorder (CV-positive group) and 153 OSAS patients without cardiovascular disorder (CVnegative group). CC, CT and TT genotype distributions between groups were similar [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); respectively, p>0.05]. MMP-9 level was significantly higher in CV-P patients (442.7±139.3 pg/mL) than in CV-N patients (364.4±165.0 pg/mL; p=0.0018). Conclusion: Our results showed that the presence of MMP-9 polymorphism was not associated with cardiovascular disease. MMP-9 level was higher in OSAS patients with cardiovascular disorders than without cardiovascular disorders. Finally, MMP-9 genotype was not associated with serum MMP-9 levels. Turkish Başlık: Kardiyovasküler Hastalığı olan ve olmayan Obstrüktif Uyku Apne Sendromlu Hastalarda Matriks Metalloproteinaz-9 Aktivitesi ile Gen Polimorfizmi Anahtar Kelimeler: Kardiyovasküler hastalıkları, MMP-9, polimorfizm, uyku apnesi, hipertansiyon Amaç: Obstrüktif uyku apne sendromu (OUAS) artmış kardiyovasküler morbidite ve mortalite ile ilişkilidir. Bu çalışmada kardiyovasküler hastalığı olan ve olmayan uyku apneli hastalarda matriks metalloproteinaz-9 (MMP-9) düzeyi ile MMP-9 gen polimorfizminin araştırılması amaçlandı. Gereç ve Yöntemler: Uykuda solunum bozukluğu teşhisi almış 209 hasta [Ortalama yaş (±SS), 47 (±12) yıl; E/K, 170/39] çalışmaya dahil edildi. Serum MMP-9 düzeyi ELISA, MMP-9 gen polimorfizmi polimeraz zincir reaksiyonu ve restriksiyon fragmanı uzunluk polimorfizmi ile DNA örneklerinde belirlendi. Hastalar kardiyovasküler hastalığı olan, KV-P grubu ve kardiyovasküler hastalığı olmayan, KV-N grubu olmak üzere iki alt gruba ayrıldı. Bulgular: Kardiyovasküler hastalığı olan (KV-P grup) 56 ve kardiyovasküler hastalığı olmayan (KV-N grup) 153 OUAS hasta tesbit edildi. Gruplar arası CC, CT ve TT genotip dağılımı benzer [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); sırasıyla, p>0.05] tesbit edildi. MMP-9 düzeyi KV-P hastalarda (442.7±139.3 pg/mL) KV-N hastalara (364.4±165.0 pg/mL) göre anlamlı (p=0.0018) yüksek saptandı. Sonuç: Bulgularımız, MMP-9 polimorfizm varlığının kardiyovasküler hastalıklarla ilişkili olmadığını gösterdi. MMP-9 düzeyi kardiyovasküler hastalığı olan OUAS'lı hastalarda kardiyovasküler hastalığı olmayanlara göre yüksek saptandı. Sonuç olarak, MMP-9 genotipi serum MMP-9 düzeyi ile ilişkili bulunmadı.

Keywords

Cardiovascular disease, MMP-9, polymorphism, sleep apnea, hypertension

Matrix Metalloproteinase-9 Level and Gene Polymorphism in Sleep Disordered Breathing Patients with or without Cardiovascular Disorders

Abstract

References

• Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, 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.
• Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J. Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep-apnea: a 7-year follow up. Am J Respir Crit Care Med 2002;166:159-65. [CrossRef]
• Leung RS, Bradley TD. Sleep apnea and cardiovascular disease. Am J Respir Crit Care Med 2001;164:2147-65.
• Brauer PR. MMPs role in cardiovascular development and disease. Front Biosci 2006;11:447-78. [CrossRef]
• Sundström J, Evans JC, Benjamin EJ, Levy D, Larson MG, Sawyer DB, et al. Regulations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study. Circulation 2004;109:2850-6. [CrossRef]
• Ye S. Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Cardiovasc Res 2006;69:636-45. [CrossRef]
• Wang L, Zhu T, Li Y. Relationship between matrix metalloproteinase-9 polymorphism and acute coronary syndrome. Journal of Nanjing Medical University 2007;21:147-50. [CrossRef]
• Tazaki T, Minoguchi K, Yokoe T, Samson KT, Minoguchi H, Tanaka A, et al. Increased levels and activity of matrix metalloproteinase-9 in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2011;170:1354-9. [CrossRef]
• Ye J, Liu H, Li Y, Liu X, Zhu J. Increased serum levels of C-reactive protein and matrix metalloproteinase-9 in obstructive sleep apnea syndrome. Chin Med J 2007;120:1482-6.
• Demacq C, de Souza AP, Machado AA, Gerlach RF, Tanus-Santos JE. Genetic polymorphism of matrix metalloproteinase (MMP)-9 does not affect plasma MMP-9 activity in healthy subjects. Clin Chim Acta 2005;365:183-7. [CrossRef]
• The Report of American Academy of Sleep Medicine. Task Force Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;5:667-89.
• Rechtschaffen A, Kales A (1968). A Manual of Standardized Terminology, Technique, and Scoring System for Sleep Stages of Human Subjects, BIS/ BRI, UCLA, Los Angeles.
• Öztürk L, Mansour B, Yüksel M, Yalçın AS, Çelikoğlu F, Gökhan N. Lipid peroxidation and osmotic fragility of red blood cells in sleep apnea patient. Clin Chim Acta 2003;332:83-8. [CrossRef]
• Gremlich S, Nguyen D, Reymondin D, Hohlfeld P, Vial Y, Witkin SS, et al. Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk. J Reprod Immunol 2007;74:143-51. [CrossRef]
• Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner D, et al. Plasma concentration and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 2003;107:1579-85. [CrossRef]
• Kaditis AG, Alexopoulos EI, Karathanasi A, Ntamagka G, Oikonomidi S, Kiropoulos TS, et al. Adiposity and low grade systemic inflammation modulate matrix metalloproteinase-9 levels in Greek children with sleep apnea. Pediatr Pulmonol 2010;45:693-9. [CrossRef]
• Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A, et al. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 1999;99:1788-94. [CrossRef]
• Opstad TB, Pettersen AAR, Weiss TW, Akra S, Ovstebo R, Arnesen H, et al. Genetic variation, gene expression and circulating levels of matrix metalloproteinase-9 in patients with stable coronary artery disease. Clin Chim Acta 2012;413:113-20. [CrossRef] Alp E, Menevse S, Tulmac M, Kan D, Yalcin R, Erkan AF, et al. Lack of association between matrix metalloproteinase-9 and endothelial nitric oxide synthase gene polymorphisms and coronary artery disease in Turkish population. DNA Cell Biol 2009;28:343-50. [CrossRef]
• Pöllanen PJ, Karhunen PJ, Mikkelsson J, Laippala P, Perola M, Penttila AM, et al. Coronary artery complicated lesion area is related to functional polymorphism of matrix metalloproteinase 9 gene: An autopsy study. Arterioscler Thromb Vasc Biol 2001;21:1446-50. [CrossRef]
• Volna J, Kemlink D, Kalousova M, Vavrova J, Majerova V, Mestek O, et al. Biochemical oxidative stress-related markers in patients with obstructive sleep apnea. Med Sci Monit 2011;17:CR491-7. [CrossRef]
• Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997;82:1313-6. [CrossRef]
• Saren P, Welgus HG, Kovanen PT. TNF-alpha and IL-1beta selectively induce expression of 92-kDa gelatinase by human macrophages. J Immunol 1996;157:4159-65. 2012; 30: 8-12