New genetic risk factors for myocardial infarction at young patients in Southern Turkey

Yıl 2020, Cilt: 45 Sayı: 1, 1 - 8, 31.03.2020

Rabia Akıllı Çağlar Emre Çağlıyan Onur Kaypaklı Mehmet Kanadaşı Mustafa Demirtaş

https://doi.org/10.17826/cumj.623510

Öz

Purpose: Genetic predisposition plays an important role in the development of atherosclerosis in young patients. The aim of this study was to determine the relationship between myocardial infarction and HLA antigens in young patients who had myocardial infarction in southern region of Turkey.
Materials and Methods: We enrolled 50 patients ( 36 male, 14 female, mean age 45.0  7.1 ) who had myocardial infarction before 45 years old in men and 55 years old in women and 50 healthy subjects (31 male, 19 female, mean age 51.5  5.5 ) as a control group into the study. Venous blood samples were collected for HLA tissue typing and determining trombogenic factors. Histocompatibility antigens (HLA-A,B,C,-DQ,-DR) were studied with Polymerase Chain Reaction (PCR)-Sequance Spesific Oligonucleotide typing (SSO) method.
Results: Frequency of HLA antigens in patients and controls were 38% and 10% for HLA-A24, 40% and 10% for HLA-DQB2, 26% and 6% for HLA-DRB1-7 and 52% and 26% for HLA-DRB4-1. Chi square test revealed a significant relation with the disease and the presence of these antigens. In the logistic regression analysis, smoking, Lp(a), homocysteine and HLA-DQB1 subtype were independently associated with development of MI in young patients.
Conclusion: The presence of HLA-A24, HLA-DQB2, HLA-DRB1-7 and HLA-DRB4-1 may be used as genetic markers for the tendency to coronary artery disease in southern region of Turkey. 

Türkiye'nin güneyinde genç hastalarda görülen miyokart enfarktüsü için yeni genetik risk faktörleri

Öz

Amaç: Genetik yatkınlık genç hastalarda ateroskleroz gelişiminde önemli rol oynamaktadır. Bu çalışmanın amacı, Çukurova bölgesinde miyokart enfarktüsü geçiren genç hastalarda miyokart enfarktüsü ile HLA antijenleri arasındaki ilişkiyi belirlemektir.
Gereç ve Yöntem: Çalışmaya 45 yaşından önce miyokart enfarktüsü geçirmiş 36 erkek ve 55 yaşından önce miyokart enfarktüsü geçirmiş 14 kadın olmak üzere (ort. yaş 45.0±7.1) toplam 50 hasta alındı. Kontrol grubu 50 sağlıklı bireyden (31 erkek, 19 kadın, ort. yaş 51.55.5) oluşturuldu. HLA doku tiplemesi ve trombojenik faktörlerin belirlenmesi için venöz kan örnekleri toplandı. HLA antijenleri (HLA-A,B,C,-DQ,-DR) Polimeraz Zincir Reaksiyonu- Sekans Spesifik Oligonükleotit tiplendirme (PCR-SSO) metodu ile çalışıldı.
Bulgular: Hasta ve kontrol grubunda HLA antijenlerinin sıklığı HLA-A24 için %38 ve %10, HLA-DQB2 için %40 ve %10, HLA-DRB1-7 için %26 ve %6 ve HLA-DRB4-1için %52 ve %26 idi. Ki-kare testi hastalıkla ve bu antijenlerin varlığı arasında anlamlı bir ilişki olduğunu ortaya koydu. Lojistik regresyon analizinde sigara kullanımı, Lp(a), homosistein ve HLA-DQB1 alt tipi genç hastalarda MI gelişimi ile bağımsız olarak ilişkiliydi.
Sonuç: Çalışma sonuçlarına göre HLA-A24, HLA-DQB2, HLA-DRB1-7 ve HLA-DRB4-1 antijenlerinin Çukurova bölgesinde koroner arter hastalığına eğilimi belirlemede genetik belirteçler olarak kullanılabileceği sonucuna varılmıştır.

Anahtar Kelimeler

Miyokart enfarktüsü, HLA

Kaynakça

• Ross R (1999) Mechanisms of Disease: Atherosclerosis - An Inflammatory Disease. N Engl J Med 340:115-126.
• Wilhelmsen L, Wedel H, Tibblin GO (1973) Multivariate analysis of risk factors for coronary heart disease. Circulation 48: 950-958.
• Neufeld HN, Goldbourt U (1983) Coronary heart disease: genetic aspects. Circulation 67: 943-954.
• Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ (1993) Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 342:1076-1079.
• Doğan Y, Ural D, Domaniç N, Yılmaz E (2001) Akut miyokard infarktüsü ile HLA doku grubu ilişkisi. Anadolu Kardiyoloji Dergisi 1: 80-84.
• Altuntaş Y, Yılmaz E, Tapan E, Hatemi H (1996) Türk toplumunda HLA dağılımı ve bazı HLA’lar ile bazı hastalıklar arasındaki ilişkiler. Endokrinolojide Yönelişler 2: 58-63.
• Ridker PM, Genest J, Libby P (2001) Risk factors for atherosclerotic disease, in: Braunwald E (ed). Heart Disease A Textbook of Cardiovascular Medicine. 6th ed, Philadelphia. W.B. Saunders Company 1010-1039.
• Barbash GI, White HD, Modan M, Diaz R, Hampton JR, et al. (1995) Acute myocardial infarction in the young – the role of smoking. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. Eur Heart J 16:313-6.
• Frei B, Forte TM, Ames BN, Cross CE (1991) Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma: Protective effects of ascorbic acid. Biochem J 277: 133.
• Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, et al. (1993) Cigarette smoking is associated with dose related and potentially reversible improvement of endothelium-dependent dilation in healthy young adults. Circulation 88: 2149
• Rival J, Riddle JM, Stein PD (1987) Effects of chronic smoking on platelet function. Thromb Res 45: 75
• Siscovick DS, Schwartz SM, Rosendaal FR, Psaty BM (1997) Thrombosis in the Young: Effect of Atherosclerotic Risk Factors on the Risk of Myocardial Infarction Associated with Prothrombotic Factors. Thrombosis and Haemostasis 78(1): 7-12.
• Gordon T, Kannel WB, McGee D, Dawber TR (1974) Death and coronary attacks in men after giving up cigarette smoking : A report from the Framingham study. Lancet 2: 1345
• Hopkins PN (1989) Williams RR. Human genetics and coronary heart disease: A public heart perspective. Annu Rev Nutr 9:303
• İliçin, Biberoğlu, Süleymanlar, Ünal (2003) İç Hastalıkları.(2nd edn), Güneş Kitabevi, 449-474
• Andreassi MG (2003) Coronary atherosclerosis and somatic mutations: an overview of the contributive factors for oxidative DNA damage. Mutat Res. 543:67-86.
• Hurt’s The Heart. Valentin Fuster, R. Wayne Alexander, Robert O’Rourke (2002) 10. Baskısının Türkçe çevirisi. And Danışmanlık Eğitim Yayıncılık ve Organizasyon Ltd. Şti (1st edn ), 1065-1109
• Rissanen AM (1979) Familial aggregation of coronary heart disesase in a high incidence area. Br Heart J 42:294
• Williams RR, Hopkins PN, Wu LL, Lalouel JM, Hunt SC (1994) Evaluating family history to prevent early coronary heart disease. In: Person TA, ed. Primer in Preventive Cardiology. Dallas: American Heart Association 93
• Solberg LA, Enger Sc, Hjermann I, Helgeland A, Leren P, et al. (1980) Risk factors for coronary and cerebral atherosclerosis in Oslo Study In Atherosclerosis V (Eds. Gotto AM, Smith LC, Allen B), New York, NY: Springer Verlag 57-62.
• Freidman M, Van den Bovenkamp G (1966) The pathogenesis of a coronary trombus. Am J Pathol 48: 19-31.
• Xu QB, Oberhuber G, Grunschwitz M, Wick G (1990) Immnology of atherosclerosis: cellular composition and major histocompatibility complex class II antigen expression in aortic intima, fatty streaks and atherosclerotic plaques in young and aged human specimens. Clin Immunol Immunopahol 56: 344-59.
• Schwartz BD (1996) The major histocompatibility complex and disease susceptibility. JC Bennett, F Plum. Cecil Textbook of Medicine. Philadelphia, W.B. Saunders Company 1430-1.
• Jonasson L, Holm J, Skalli O, Gabbiani G, Hansson GK (1985) Expression of class II transplantation antigen on vascular smooth muscle cells in human atherosclerosis. J Clin Invest 76: 125-31.
• Van der Wal AC, Das PK, Tigges AJ, Becker AE (1992) Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol 141: 1427-33.
• Frostegard J, Wu R, Giscombe R, Holm G, Lefvert AK, et al. (1992) Induction of T-cell activation by oxidized low density lipoprotein. Arterioscler Thromb 12: 461-7.27. Van der Wal AC, Becker AE, van der Loos CM, Das PK (1994) Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inşammatory process irrespective of the dominant plaque morphology. Circulation 89: 36-44.
• Hansson GK, Jonasson L, Holm J, Claesson-Welsh L (1986) Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant gamma chain. Clin Exp Immunol 64: 261-8.
• Swanberg M, Lidman O, Padyukov L et al. (2005) MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat Genet 37:486–94.
• Porto I, Leone AM, Crea F, Andreotti F (2005) Inflammation, genetics, and ischemic heart disease: focus on the majör histocompatibility complex (MHC) genes. Cytokine 29: 187–96.
• Palikhe A, Sinisalo J, Seppanen M, Valtonen V, Nieminen MS, et al. (2007) Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease. Tissue Antigens 69:47–55.
• Björkbacka H, Lavant E.H, Fredrikson G.N, Melander O, Berglund G, et al. (2010) Weak associations between human leucocyte antigen genotype and acute myocardial infarction. Journal of Internal Medicine 268:50–58.
• Stone PH, Sherrid MV, Cohn KE (1981) Correlation of HLA types in premature coronary artery disease: an attempt to define independent genetic risk factors. Chest 79: 381-5.
• Logan RL, Oliver MF, Mc Tavish J, Darg C, White AG (1977) Histocompatibility antigens and myocardial infarction. Tissue Antigens 10: 361-3.
• Scott BB, Mc Guffin P, Rajah SM, Stoker JB, Losowsky MS (1976) Histocompatibility antigens and myocardial infarction. Tissue Antigens 7: 187-8.
• Khaitov RM, Polianskaia IS, Alekseev LP (1990) The HLA system antigens in patients with cardiovascular diseases. Ter Arkh 62: 70-4.
• Balliuzek MF, Serova LD (1984) Immunogenetic characteristics of patients with ischemic heart disease. Kardiologiia 24: 77-81.
• Sewdarsen M, Hammond MG, Vythilingum S, Appadoo B (1987) Histocompatibility antigens in Indian patients with myocardial infarction. Tissue Antigens 29: 21-5.
• Jonasson L, Eriksson T, Dahlen GH, Lindblom B (1997) Lp (a) and HLA-DRB1 and -DQB1 genes in coronary artery disease. Atherosclerosis 133: 111-4.
• Şentürk H, Bağrıaçık N, Üstün Ü (1984) Ünsüline bağımlı diyabetes mellitus etyolojisinde HLA sistemi. Cerrahpaşa Tıp Fakültesi Dergisi 15: 532-7.