Effect of Interleukin-6 promoter polymorphisms in survivors of myocardial infarction and matched controls in the North and South of Europe. The HIFMECH Study.
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.
Kelberman
Daniel
D
Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, UK.
Hawe
E
E
Luong
L A
LA
Mohamed-Ali
Vidya
V
Lundman
Pia
P
Tornvall
Per
P
Aillaud
M F
MF
Juhan-Vague
Irène
I
Yudkin
John S
JS
Margaglione
Maurizio
M
di Minno
Giovanni
G
Tremoli
Elena
E
Humphries
Stephen E
SE
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
D015415:Biomarkers; D015850:Interleukin-6