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世界核心医学期刊文摘(神经病学分册) 2006年第4期 10-10页

作者： pawlikowska l. W.l. Young 江山 University of Cal.fornia at San Francisco 1001 Potrero Avenue San Francisco CA United StatesDr

We recentl. reported that the GG genotype of the interl.ukin- 6 (Il. 6)- 174G > C promoter pol.morphism is associated with cl.nical.presentation of intracranial.hemorrhage in brain arteriovenous mal.ormation (AVM) patients. In this study, we investigated whether tissue Il. 6 expression was associated with Il. 6- 174G > C genotype, and whether Il. 6 was l.nked to downstream targets invol.ed in angiogenesis and vascul.r instabil.ty. Our resul.s showed that the highest Il. 6 protein l.vel. in brain AVM tissue were associated with Il. 6- 174GG genotype (GG: 57.7 ± 20.2; GC: 35.6 ± 26.6; CC: 13.9 ± 10.2 pg/mg; p = 0.001). Il. 6 protein l.vel. were increased in AVM tissue from patients with hemorrhagic presentation compared with patients without hemorrhage (55 ± 22 vs 40 ± 27 pg/mg; p = 0.038). Il. 6 messenger RNA expression strongl. correl.ted with messenger RNA l.vel. of Il. 1β , tumor necrosis factor- α , Il. 8, matrix metal.oproteinase- 3 (MMP- 3), MMP- 9, and MMP- 12. We further investigated the pl.usibil.ty of Il. 6 being an upstream cytokine responsibl. for initiating the angiogenic cascade by cel. cul.ure and animal.experiments. Il. 6 induced MMP- 3 and MMP- 9 expression and activity in mouse brain and increased prol.feration and migration of cerebral.endothel.al.cel.s. Together, our resul.s suggest that the Il. 6 genotype associated with intracranial.hemorrhage modul.tes Il. 6 expression in brain AVM tissue, which is consistent with the hypothesis that infl.mmatory processes induce angiogenic activity possibl. contributory to brain AVM intracranial.hemorrhage.

关键词：白介素脑动静脉畸形脑内出血

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世界核心医学期刊文摘(神经病学分册) 2006年第2期 60-60页

作者： pawlikowska l. Tran M.N. Achrol.A.S. W.l. Young 张慧 UCSF 1001 Potrero Ave. SanFrancisco CA 94110 United States.Dr

Background and Purpose -Mutations in endogl.n (ENG)-and activin-l.ke kinase (Al.1) cause hereditary hemorrhagic tel.ngiectasias, disorders characterized by pul.onary and brain arteriovenous mal.ormations (BAVMs). We investigated whether pol.morphisms in these genes are al.o associated with sporadic BAVM. Methods -A total.of 177 sporadic BAVM patients and 129 control. (al. subjects white) were genotyped for 2 variants in Al.1 and 7 variants in ENG. Resul.s -The Al.1 IVS3-35A>G pol.morphism was associated with BAVM: (AnyA [AA+AG] genotype: odds ratio, 2.47; 95%CI, 1.38 to 4.44; P=0.002). Two ENG pol.morphisms, ENG -1742A >G and ENG 207G >A, showed a trend toward association with BAVM that did not reach statistical.significance. Concl.sions -A common pol.morphism in Al.1 is associated with sporadic BAVM, suggesting that genetic variation in genes mutated in famil.al.BAVM syndromes may pl.y a rol. in sporadic BAVMs.

关键词：散发性 Al.1 多态性 ENG

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