Carrier-state of D allele in ACE gene insertion deletion polymorphism is associated with coronary artery disease, in contrast to the C677-T transition in the MTHFR gene

• Autorzy: Zak I. , Niemiec P. , Sarecka B. , Balcerzyk A. , Ciemniewski Z. , Rudowska E. , Dylag S.
• Języki publikacji: EN

Abstrakty

EN

Angiotensin I-converting enzyme (ACE), which plays an important role in blood pressure regulation, and methylenetetrahydrofolate reductase (MTHFR) involved in homocysteine metabolism belong to a large group of polypeptides which may be po­tential risk factors for atherosclerosis and coronary artery disease (CAD). To assess whether polymorphisms of the genes encoding these peptides are associated with CAD in Silesian we conducted a study among 68 individuals suffering from CAD (in­cluding 52 cases after myocardial infarction), 51 subjects with positive family history of CAD and 111 controls. We analysed the distribution of genotypes and allele fre­quencies of the insertion/deletion (I/D) polymorphism in the ACE gene using PCR am­plification, and the C677^T polymorphism in the MTHFR gene using PCR-RFLP analysis. We found that D allele frequency was significantly higher in CAD patients (61%) than in controls (43%) (P = 0.001, OR = 2.06). The D allele carriers (DD + ID geno­types) were more frequent in the CAD patients (85%) compared to control group (65%) (P = 0.003, OR = 3.14), whereas the familial CAD risk group shows the highest frequency of the ID genotype (57% vs 43% in controls). In contrast, the MTHFR polymorphism does not seem to be associated with the disease. Our data indicate that in Silesian CAD patients the disease is strongly associated with carrier-state of the ACE D allele, but not with the C677->T transition in the MTHFR gene.

Słowa kluczowe

EN

coronary artery disease; angiotensin converting enzyme gene; polymorphism; deletion; cardiology; methylenetetrahydrofolate reductase gene; gene insertion

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2003
• Tom: 50
• Numer: 2
• Opis fizyczny: p.527-534,fig.

Twórcy

autor

Zak I.

• Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland

autor

Niemiec P.

autor

Sarecka B.

autor

Balcerzyk A.

autor

Ciemniewski Z.

autor

Rudowska E.

autor

Dylag S.

Bibliografia

• Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. (2000)
• ACE gene polymorphism in cardiovascular disease. Meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol.; 20: 484-92.
• Arbustini E, Grasso M, Fasani R, Klersy C, Diegoli M, Porcu E, Banchieri N, Fortina P, Danesino C, Specchia G. (1995) Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction. Br Heart J.; 74: 584-91.
• Ballantyne CM, Abe Y. (1997) Molecular markers of atherosclerosis. J Cardiovasc Risk.; 4: 353-6.
• Beohar N, Damaraju S, Prather A, Yu QT, Raizner A, Kleiman NS, Roberts R, Marian AJ. (1995) Angiotensin-I converting enzyme is a risk factor for coronary artery disease. JInvestigMed.; 43: 275-80.
• Bohn M, Berge KE, Bakken A, Erikssen J, Berg K. (1993) Insertion/deletion (I/D) polymorphism at the locus for angiotensin-converting enzyme and parental history of myocardial infarction. Clin Genet.; 44: 298-301.
• Brugada R, Marian AJ. (1997) A common mutation in methylenetetrahydrofolate reductase is not major risk of coronary artery disease or myocardial infarction. Atherosclerosis.; 128: 107-12.
• Cambien F. (1999) Genetic prediction of myocardial infarction. Blood Coagul Fibrinolysis.; 10: S23-S24.
• Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature.; 359: 641-4.
• Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I. (1991) Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med.; 324: 1149-55.
• Friedewald WT, Levy RI, Fredrickson DS. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of preparative centrifuge. Clin Chem.; 18: 499-502.
• Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet.; 10: 111-3.
• Goracy I. (2000) Polymorphism of genes coding angiotensin I converting enzyme and metylenetetrahydrofolate reductase in patients with ischemic heart disease. Ann Acad Med Stetin.; 46: 97-108.
• Gulec S, Aras O, Akar E, Tutar E, Omurlu K, Avci F, Dincer I, Akar N, Oral D. (2001) Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction. Clin Cardiol.; 24: 281-4.
• Libby P, Ridker PM, Maseri A. (2002) Inflammation and atherosclerosis. Circulation.; 105: 1135-43.
• Marian AJ. (1997) Genetic markers: genes involved in atherosclerosis. J Cardiovasc Risk.; 4: 333-9.
• Nakai K, Fusazaki T, Suzuki T, Ohsawa M, Ogiu N, Kamata J, Kawazoe K, Nakai K, Itoh C, Yanagisawa M, Ishida T, Hiramori K. (2000) Genetic polymorphism of 5,10-methylenetetrahydrofolate increases risk of myocardial infarction and is correlated to elevated levels of homocysteine in the Japanese general population. Coron Artery Dis.; 11: 47-51.
• Ou T, Yamakawa-Kobayashi K, Arinami T, Amemiya H, Fujiwara H, Kawata K, Saito M, Kikuchi S, Noguchi Y, Sugishita Y, Hamaguchi H. (1998) Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case-control study. Atherosclerosis.; 137: 23-8.
• Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest.; 86: 1343-6.
• Ross R. (1999) Atherosclerosis an inflammatory disease. N Engl J Med.; 340: 115-26.
• Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P. (1994) Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci US A.; 91: 3662-5.
• Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Suzuki Y, Mezzano S, Plaza JJ, Egido J. (2001) Role of renin- angiotensin system in vascular diseases. Hypertension.; 38: 1382-93.
• Trzeciak T, Szymczynska-Mullauer A, Kwiatkowska J, Horst A, Slomski R. (1996) Analiza polimorfizmu genu konwertazy angiotensynowej (ACE) u chorych z zawalem miesnia sercowego. Pol Arch Med Wewn; 95: 35-40.
• Wang XL, McCredie RM, Wilcken DE. (1996) Genotype distribution of angiotensin-converting enzyme polymorphism in Australian healthy and coronary populations and relevance to myocardial infarction and coronary artery disease. Arterioscler Thromb Vasc Biol.; 16: 115-9.