Proinflammatory Genetic Profiles in Subjects With History of Ischemic Stroke

Stroke - Tập 35 Số 10 - Trang 2270-2275 - 2004
Andrea Flex1, Eleonora Gaetani1, Pierangelo Papaleo1, Giuseppe Straface1, Anna Proia1, Giovanni Pecorini1, Paolo Tondi1, Paolo Pola1, Roberto Pola1
1From the Laboratory of Vascular Biology and Genetics (A.F., E.G., P.Papaleo, G.S., A.S.P., G.P., P.Pola, R.P.) and the Department of Medicine (A.F., E.G., P.Papaleo, G.S., A.S.P., G.P., P.T., P.Pola, R.P.), A. Gemelli University Hospital, Università Cattolica del Sacro Cuore, School of Medicine, Rome, Italy.

Tóm tắt

Background and Purpose— Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins. Methods— The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls. The polymorphisms of the C-reactive protein ( CRP ), interleukin-6 ( IL-6 ), macrophage migration inhibitory factor ( MIF ), monocyte chemoattractant protein-1 ( MCP-1 ), intercellular adhesion molecule-1 ( ICAM-1 ), E-selectin ( E-sel ), and matrix metalloproteinase-3 ( MMP-3 ) genes were studied. Results— IL-6 GG, IL-6 GC, MCP-1 GG, ICAM-1 EE, E-sel AA, and MMP-3 5A5A genotypes were significantly and independently associated with stroke history. The odds of stroke increased with the number of high-risk genotypes: carrying 1 proinflammatory gene variant conferred a risk of 3.3 (1.6 to 6.9), whereas individuals concomitantly carrying 2 and 3 proinflammatory gene variants had adjusted odds ratios of 21.0 (7.6 to 57.5) and 50.3 (10.2 to 248.1), respectively. Conclusions— Proinflammatory genetic profiles are significantly more common in subjects with stroke history. Synergistic effects between proinflammatory genotypes might be potential markers for cerebrovascular diseases.

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Tài liệu tham khảo

10.1046/j.1365-2796.2002.01019.x

10.1161/atvb.18.4.503

10.1161/01.str.0000021902.33129.69

10.1161/01.cir.0000012942.49244.82

Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995; 92: 1565–1569.

10.1093/hmg/ddh039

10.1016/S0195-668X(03)00313-0

10.1161/01.str.0000062346.70983.df

10.1161/circ.99.21.2717

10.1002/1529-0131(200109)44:9<2211::AID-ART375>3.0.CO;2-A

10.1172/JCI2629

10.1002/art.10882

10.1016/S0021-9150(01)00703-1

10.1016/0092-8674(88)90434-5

10.1161/01.atv.0000067427.40133.59

10.1038/sj.gene.6364036

10.1016/S0016-5085(03)00899-0

10.1007/BF00831996

10.1086/318789

10.1007/s100380050022

10.1002/1529-0131(200108)44:8<1782::AID-ART314>3.0.CO;2-#

10.1016/S0167-5273(02)00073-6

10.1034/j.1399-0039.2001.580508.x

10.1161/atvb.20.6.1600

10.1006/bbrc.1999.0796

10.1074/jbc.271.22.13055

10.1016/0092-8674(90)90805-O

10.1016/S0021-9150(01)00423-3

10.1053/ejvs.2002.1711

10.1097/00001721-200209000-00002

10.1016/S0531-5565(02)00031-1

10.1016/S0735-1097(03)00482-0

10.1097/01.ASN.0000015609.31253.7F

10.1042/bj2650621

10.4049/jimmunol.165.8.4658

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Stroke

Tập 35 Số 10

2270-2275

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