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The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

, Daniel I Swerdlow, Michael V Holmes

    Lancet (London, England)
    |March 17, 2012
    PubMed

    Insights

    Interleukin-6 receptor (IL6R) blockade shows promise for preventing coronary heart disease. Genetic analysis suggests IL6R signaling plays a causal role, supporting IL6R blockade as a potential therapeutic strategy.

    Area of Science:

    • Cardiovascular Genetics
    • Immunology
    • Pharmacology

    Background:

    • High interleukin-6 (IL-6) levels increase coronary heart disease (CHD) risk.
    • Tocilizumab, an IL-6 receptor (IL6R) blocker, treats rheumatoid arthritis but its effect on CHD is unknown.

    Purpose of the Study:

    • To evaluate the efficacy and safety of IL6R inhibition for primary prevention of CHD using Mendelian randomization.
    • To compare genetic findings with tocilizumab's effects in rheumatoid arthritis trials.

    Main Methods:

    • Mendelian randomization utilizing single nucleotide polymorphisms (SNPs) in the IL6R gene.
    • Comparison of genetic associations with tocilizumab's effects from randomized trials.

    Main Results:

    • An IL6R SNP (rs7529229) was linked to higher IL-6 and lower C-reactive protein and fibrinogen levels.
    • This SNP was associated with a reduced odds of coronary heart disease events (OR 0.95, P=1.53×10⁻⁵).
    • Genetic findings mirrored tocilizumab's anti-inflammatory effects observed in rheumatoid arthritis patients.

    Conclusions:

    • IL6R signaling appears to causally contribute to coronary heart disease development.
    • IL6R blockade may offer a novel therapeutic approach for CHD prevention, warranting further randomized trials.
    • Population genetic studies can aid in validating drug targets and repurposing medications.
    Abstract

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