eNOS G894T polymorphism as a mild predisposing factor for abdominal aortic aneurysm

被引:34
作者
Fatini, C
Sofi, F
Sticchi, E
Bolli, P
Sestini, I
Falciani, M
Azas, L
Pratesi, G
机构
[1] Univ Florence, Dept Med & Surg Crit Care, Thrombosis Ctr, Azienda Osped Univ Careggi, I-50134 Florence, Italy
[2] Univ Florence, Ctr Study Mol & Clin Level Chron Degenerat & Neop, I-50121 Florence, Italy
[3] Univ Florence, Dept Med & Surg Crit Care, Unti Vasc Surg, Florence, Italy
关键词
D O I
10.1016/j.jvs.2005.05.044
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective: Abdominal aortic aneurysm (AAA) represents a chronic degenerative condition associated with atherosclerosis. Actually, data from experimental and clinical studies suggest that nitric oxide (NO) is a modulator in maintaining endothelial function and antithrombotic intravascular environment. Reduced vascular NO generation in subjects carrying the rare variants of the eNOS gene might predispose to AAA. No information is available about the influence of the eNOS gene T-786C, G894T, and 4a/4b polymorphisms in the susceptibility to the disease. Methods: In this study we evaluated the role of these polymorphisms in the predisposition to AAA and their influence in hypertensive and normotensive patients. We studied 250 consecutive patients with AAA referred to the Unit of Vascular Surgery of the University of Florence compared with 250 truly healthy subjects with a negative history of vascular diseases. All subjects, patients, and controls, underwent duplex scanning examination, and to assess the presence of other atherosclerotic localizations, all patients underwent clinical and instrumental examinations. Results: A significant difference in genotype distribution and allele frequency was observed for eNOS G894T but not for T-786C and 4a/4b polymorphisms. At the multivariate analysis after adjustment for traditional vascular risk factors and other atherosclerotic localizations, the eNOS 894T variant was significantly associated with AAA, according to dominant and recessive models (dominant model odds ratio [OR]: 2.2, 95% confidence interval [Cl]: 1.21-3.93, P = .007; recessive model OR: 2.7, 95% CI: 1.42- 5.20, P = .002). When patients with other atherosclerotic localizations were excluded from the analysis, the 894T variant still remained associated with the predisposition to AAA, according to the models considered (dominant model OR: 2.1, 95% CI: 1.23-3.92, P = .007; recessive model OR: 2.8, 95% CI: 1.45-5.24, P = .002). Conclusions. The present study showed that the eNOS G894T polymorphism is a mild modulator of the predisposition to AAA apart from traditional risk factors, suggesting a genetic influence on the molecular mechanisms responsible for this complex disease.
引用
收藏
页码:415 / 419
页数:5
相关论文
共 23 条
[1]   Nitric oxide and arterial disease [J].
Barbato, JE ;
Tzeng, E .
JOURNAL OF VASCULAR SURGERY, 2004, 40 (01) :187-193
[2]  
Barnett HJM, 2002, CAN MED ASSOC J, V166, P1169
[3]  
*ESH ESC HYP GUID, 2003, J HYPERTENS, V21, P1779
[4]   NITRIC OXIDE-GENERATING VASODILATORS AND 8-BROMO-CYCLIC GUANOSINE-MONOPHOSPHATE INHIBIT MITOGENESIS AND PROLIFERATION OF CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS [J].
GARG, UC ;
HASSID, A .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (05) :1774-1777
[5]   Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report [J].
Grundy, SM ;
Becker, D ;
Clark, LT ;
Cooper, RS ;
Denke, MA ;
Howard, WJ ;
Hunninghake, DB ;
Illingworth, R ;
Luepker, RV ;
McBride, P ;
McKenney, JM ;
Pasternak, RC ;
Stone, NJ ;
Van Horn, L ;
Brewer, HB ;
Cleeman, JI ;
Ernst, ND ;
Gordon, D ;
Levy, D ;
Rifkind, B ;
Rossouw, JE ;
Savage, P ;
Haffner, SM ;
Orloff, DG ;
Proschan, MA ;
Schwartz, JS ;
Sempos, CT ;
Shero, ST ;
Murray, EZ ;
Keller, SA ;
Jehle, AJ .
CIRCULATION, 2002, 106 (25) :3143-3421
[6]   A common variant of the endothelial nitric oxide synthase (Glu298→Asp) is a major risk factor for coronary artery disease in the UK [J].
Hingorani, AD ;
Liang, CF ;
Fatibene, J ;
Lyon, A ;
Monteith, S ;
Parsons, A ;
Haydock, S ;
Hopper, RV ;
Stephens, NG ;
O'Shaughnessy, KM ;
Brown, MJ .
CIRCULATION, 1999, 100 (14) :1515-1520
[7]   The T-786→C mutation in endothelial nitric oxide synthase is associated with hypertension [J].
Hyndman, ME ;
Parsons, HG ;
Verma, S ;
Bridge, PJ ;
Edworthy, S ;
Jones, C ;
Lonn, E ;
Charbonneau, F ;
Anderson, TJ .
HYPERTENSION, 2002, 39 (04) :919-922
[8]   Genetic and environmental determinants of plasma nitrogen oxides and risk of ischemic heart disease [J].
Jeerooburkhan, N ;
Jones, LC ;
Bujac, S ;
Cooper, JA ;
Miller, GJ ;
Vallance, P ;
Humphries, SE ;
Hingorani, AD .
HYPERTENSION, 2001, 38 (05) :1054-1061
[9]   SUGGESTED STANDARDS FOR REPORTING ON ARTERIAL ANEURYSMS [J].
JOHNSTON, KW ;
RUTHERFORD, RB ;
TILSON, MD ;
SHAH, DM ;
HOLLIER, L ;
STANLEY, JC .
JOURNAL OF VASCULAR SURGERY, 1991, 13 (03) :452-458
[10]   Allele frequency of human endothelial nitric oxide synthase gene polymorphism in abdominal aortic aneurysm [J].
Kotani, K ;
Shimomura, T ;
Murakami, F ;
Ikawa, S ;
Kanaoka, Y ;
Ohgi, S ;
Adachi, K ;
Nanba, E .
INTERNAL MEDICINE, 2000, 39 (07) :537-539