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Interleukin-6 -174G > C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS)

Basso, F; Lowe, GDO; Rumley, A; McMahon, AD; Humphries, SE; WOSCOPS Grp,; (2002) Interleukin-6 -174G > C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS). ARTERIOSCL THROM VAS , 22 (4) 599 - 604. 10.1161/01.ATV.00000132783.84306.lA.

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Abstract

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 CHID risk, We have studied the contribution of these polymorphisms to CHID 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 CHID. 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% Cl 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 CHID. These results demonstrate the importance of the inflammatory system in determining the risk of CHID and support the nonlipid effect of statins on risk.

Type:Article
Title:Interleukin-6 -174G > C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS)
DOI:10.1161/01.ATV.00000132783.84306.lA
Keywords:interleukin-6, genetic polymorphisms, inflammation, pravastatin, coronary heart disease, C-REACTIVE PROTEIN, APPARENTLY HEALTHY-MEN, CARDIOVASCULAR-DISEASE, PROMOTER POLYMORPHISM, MYOCARDIAL-INFARCTION, PLASMA-CONCENTRATION, REDUCTASE INHIBITOR, ARTERY DISEASE, MESSENGER-RNA, GENE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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