title: Effect of Interleukin-6 promoter polymorphisms in survivors of myocardial infarction and matched controls in the North and South of Europe. The HIFMECH Study.
abstract: Elevated plasma IL-6 levels have been implicated in the pathogenesis of coronary heart disease. We have investigated the association of two polymorphisms in the promoter of IL-6 (-572G>C and -174G>C) with levels of inflammatory markers and risk of myocardial infarction (MI) in a European study of MI survivors and age-matched controls from two high-risk centres in the North of Europe, and two low risk centres in the South. IL-6 and CRP levels were similar in controls in both regions, but were higher in cases. For the -174G>C polymorphism the rare -174C allele showed a regional difference in allele frequency, being more common in the North European group (0.43 vs 0.28; p < 0.0005), where -174C allele carriers showed an apparent reduced risk of MI compared to -174GG homozygotes (OR 0.53, 95%CI 0.32, 0.86). No such effect was observed in the South or with the -572G>C in either group. Neither genotype was associated with a significant effect on plasma IL-6 levels in either cases or controls. Furthermore, no regional difference was observed in the frequency of the -572G>C SNP, suggesting that these polymorphisms are unlikely to be contributing to the observed increased risk of cardiovascular disease in Northern Europe.
authors.affiliation: Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kelberman
authors.forename: E
authors.initials: E
authors.lastname: Hawe
authors.forename: L A
authors.initials: LA
authors.lastname: Luong
authors.forename: Vidya
authors.initials: V
authors.lastname: Mohamed-Ali
authors.forename: Pia
authors.initials: P
authors.lastname: Lundman
authors.forename: Per
authors.initials: P
authors.lastname: Tornvall
authors.forename: M F
authors.initials: MF
authors.lastname: Aillaud
authors.forename: Irène
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: John S
authors.initials: JS
authors.lastname: Yudkin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
authors.forename: Giovanni
authors.initials: G
authors.lastname: di Minno
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000175:diagnosis; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D017741:Survivors; D019371:Topography, Medical
chemical_list: D015415:Biomarkers; D015850:Interleukin-6