Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of Scotland coronary prevention study (WOSCOPS).
Interleukin (IL)-6 plays an important role in the pathogenesis of coronary heart disease (CHD). Two functional polymorphisms in the IL-6 promoter have been identified (-174G>C and -572G>C), with both the rare alleles being associated with higher plasma levels of IL-6 after bypass surgery and one of them (-174G>C) associated with CHD risk. We have studied the contribution of these polymorphisms to CHD risk in the West of Scotland Coronary Prevention Study (WOSCOPS), a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHD. Four hundred ninety-eight cases (consisting of individuals experiencing a cardiovascular event during 4.8 years of follow-up) and 1109 controls (individuals matched for age and smoking habits) were genotyped. In the placebo group, there was no significant evidence of higher risk associated with the -174CC genotype compared with the GG+GC group. However, in the pravastatin-treated group, CC homozygotes had a significantly lower risk of CHD compared with the GG+GC placebo group (odds ratio 0.46, 95% CI 0.27 to 0.79), and this remained statistically significant after adjustment for classic risk factors. Compared with the GG+GC group, men with the CC genotype had modestly, but not significantly, higher baseline levels of IL-6, C-reactive protein, or fibrinogen but showed a significantly greater fall in LDL cholesterol with statin treatment (P=0.036). The -572G>C polymorphism was not significantly associated with any plasma trait or CHD risk. Thus, in subjects under pravastatin treatment, the -174CC genotype was associated with a lower risk of CHD. These results demonstrate the importance of the inflammatory system in determining the risk of CHD and support the nonlipid effect of statins on risk.
Basso
Federica
F
Centre for Cardiovascular Genetics, BHF Laboratories, Royal Free and University College London Medical School, London, UK.
Lowe
Gordon D O
GD
Rumley
Ann
A
McMahon
Alex D
AD
Humphries
Steve E
SE
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein; D017035:Pravastatin