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Genetic Variation in the Interleukin‐10 Gene Promoter and Risk of Coronary and Cerebrovascular Events
Author(s) -
TROMPET S.,
PONS D.,
DE CRAEN A. J. M.,
SLAGBOOM P.,
SHEPHERD J.,
BLAUW G. J.,
MURPHY M. B.,
COBBE S. M.,
BOLLEN E.L.E.M.,
BUCKLEY B. M.,
FORD I.,
HYLAND M.,
GAW A.,
MACFARLANE P. W.,
PACKARD C. J.,
NORRIE J.,
PERRY I. J.,
STOTT D. J.,
SWEENEY B. J.,
TWOMEY C.,
WESTENDORP R. G. J.,
JUKEMA J. W.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1395.018
Subject(s) - proinflammatory cytokine , pravastatin , single nucleotide polymorphism , haplotype , medicine , allele , genome wide association study , immunology , tumor necrosis factor alpha , interleukin , bioinformatics , genetics , biology , gene , inflammation , genotype , cholesterol , cytokine
: Proinflammatory cytokines, like interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α), are implicated in the development of atherosclerosis. The role of anti‐inflammatory cytokines, like IL‐10, is largely unknown. We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL‐10 gene (4259AG, −1082GA, −592CA, and −2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the −592A variant allele) and risk of coronary events ( P = 0.019). Moreover, analysis of separate SNPs found a significant association between −2849AA carriers with incident stroke (HR (95%CI) 1.50 (1.04–2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti‐inflammatory cytokines may play an important role.