BACKGROUND: Inflammatory cytokines including the IL-1 family, TNF-alpha and IL-6 mediate the formation of thrombosis on the luminal surface of atherosclerotic plaques. Gene polymorphisms that regulate these cytokines' expression may explain part of the variation in susceptibility to stroke in patients with carotid atherosclerosis. The aim of this study was to evaluate the role of single-nucleotide polymorphisms (SNPs) and haplotypes in inflammatory genes as they relate to symptomatic carotid atherosclerosis. METHODS: The study included 95 subjects with symptomatic (transient ischaemic attacks or stroke) and 113 subjects with asymptomatic carotid atherosclerotic disease. A panel of evenly spaced SNPs including previously reported functionally significant polymorphisms were genotyped for IL-1beta (10 SNPs), IL-1alpha (nine SNPs), IL-1RN (11 SNPs), IL-6 (seven SNPs) and TNF-alpha and TNF-beta (seven SNPs). RESULTS: Using single SNP analysis, IL-1RN rs315934 (P=0.025), IL-1RN rs315946 (P=0.042), IL-1RN rs315921 (P=0.035), IL-6 rs1180243 (P=0.018) and IL-1alpha rs2071373 (P=0.025) were associated with decreased odds of symptomatic carotid disease. Additionally, two diplotypes of the IL-1RN gene (P=0.023 and 0.0064) and one diplotype in the IL-1alpha gene (P=0.02) were associated with a protective affect from cerebral ischaemic events. Logistic analysis for interaction of the protective SNPs reveals an additive effect of all SNP pair combinations. CONCLUSION: These results suggest that genetic polymorphisms in proinflammatory genes may contribute to interindividual differences in the development of symptomatic carotid atherosclerotic disease.
BACKGROUND: Inflammatory cytokines including the IL-1 family, TNF-alpha and IL-6 mediate the formation of thrombosis on the luminal surface of atherosclerotic plaques. Gene polymorphisms that regulate these cytokines' expression may explain part of the variation in susceptibility to stroke in patients with carotid atherosclerosis. The aim of this study was to evaluate the role of single-nucleotide polymorphisms (SNPs) and haplotypes in inflammatory genes as they relate to symptomatic carotid atherosclerosis. METHODS: The study included 95 subjects with symptomatic (transient ischaemic attacks or stroke) and 113 subjects with asymptomatic carotid atherosclerotic disease. A panel of evenly spaced SNPs including previously reported functionally significant polymorphisms were genotyped for IL-1beta (10 SNPs), IL-1alpha (nine SNPs), IL-1RN (11 SNPs), IL-6 (seven SNPs) and TNF-alpha and TNF-beta (seven SNPs). RESULTS: Using single SNP analysis, IL-1RNrs315934 (P=0.025), IL-1RNrs315946 (P=0.042), IL-1RNrs315921 (P=0.035), IL-6rs1180243 (P=0.018) and IL-1alphars2071373 (P=0.025) were associated with decreased odds of symptomatic carotid disease. Additionally, two diplotypes of the IL-1RN gene (P=0.023 and 0.0064) and one diplotype in the IL-1alpha gene (P=0.02) were associated with a protective affect from cerebral ischaemic events. Logistic analysis for interaction of the protective SNPs reveals an additive effect of all SNP pair combinations. CONCLUSION: These results suggest that genetic polymorphisms in proinflammatory genes may contribute to interindividual differences in the development of symptomatic carotid atherosclerotic disease.
Authors: H J M Barnett; D W Taylor; R B Haynes; D L Sackett; S J Peerless; G G Ferguson; A J Fox; R N Rankin; V C Hachinski; D O Wiebers; M Eliasziw Journal: N Engl J Med Date: 1991-08-15 Impact factor: 91.245
Authors: L Iacoviello; A Di Castelnuovo; M Gattone; A Pezzini; D Assanelli; R Lorenzet; E Del Zotto; M Colombo; E Napoleone; C Amore; A D'Orazio; A Padovani; G de Gaetano; P Giannuzzi; M B Donati Journal: Arterioscler Thromb Vasc Biol Date: 2004-11-11 Impact factor: 8.311
Authors: Sylvia Wassertheil-Smoller; Qibin Qi; Tushar Dave; Braxton D Mitchell; Rebecca D Jackson; Simin Liu; Ki Park; Joel Salinas; Erin C Dunn; Enrique C Leira; Huichun Xu; Kathleen Ryan; Jordan W Smoller Journal: Stroke Date: 2018-02-08 Impact factor: 7.914
Authors: Cecília Durães; Carla S Moreira; Inês Alvelos; Adélia Mendes; Liliana R Santos; José Carlos Machado; Miguel Melo; César Esteves; Celestino Neves; Manuel Sobrinho-Simões; Paula Soares Journal: PLoS One Date: 2014-08-15 Impact factor: 3.240
Authors: Thomas J Degraba; Gerard T Hoehn; Paul A Nyquist; Honghui Wang; Ray Kenney; Denise A Gonzales; Steven J Kern; Sai-Xia Ying; Peter J Munson; Anthony F Suffredini Journal: Cerebrovasc Dis Extra Date: 2011-12-03