Genetic IL-6 Signaling Modifies Incident Coronary Artery Disease Risk in Chronic Kidney Disease

Zhi Yu; Seyedeh Maryam Zekavat; Michael C. Honigberg; Pradeep Natarajan

doi:10.1016/j.jacc.2021.11.020

January 24, 2022Journal of the American College of CardiologyOpen Access

Genetic IL-6 Signaling Modifies Incident Coronary Artery Disease Risk in Chronic Kidney Disease

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Why the study?

Does genetic variation mimicking IL-6 inhibition (IL6R p.Asp358Ala) modify the risk of incident coronary artery disease associated with chronic kidney disease in unrelated individuals without prevalent CAD?

Structured PICO

Does genetic variation mimicking IL-6 inhibition (IL6R p.Asp358Ala) modify the risk of incident coronary artery disease associated with chronic kidney disease in unrelated individuals without prevalent CAD?

P

Population

437,014 unrelated individuals (less than 3rd degree relatedness) without prevalent coronary artery disease (CAD) in the UK Biobank, including 1,226 participants with chronic kidney disease (CKD) at baseline and 11,150 (2.6%) who developed incident CKD during follow-up.

I

Intervention

Naturally occurring genetic variation in the IL-6 receptor gene (IL6R p.Asp358Ala variant) mimicking the effect of IL-6 inhibition

C

Comparator

Wild type IL6R genotype

O

Outcome

Incident coronary artery disease (CAD), defined as self-reported, hospitalization with or death due to myocardial infarction, or hospitalization with OPCS4 codes for coronary artery bypass grafting or coronary angioplasty, over an 11.1-year median follow-up.composite

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Implication

Genetic attenuation of IL-6 signaling via the IL6R p.Asp358Ala variant significantly mitigates the heightened risk of incident coronary artery disease associated with chronic kidney disease, supporting clinical trials of selective IL-6 blockade in CKD patients.

Abstract

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Cite This Study

Yu et al. (2022) studied this question.

synapsesocial.com/papers/6aefe95aa2d1e27515269053 https://doi.org/10.1016/j.jacc.2021.11.020

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Genetic IL-6 Signaling Modifies Incident Coronary Artery Disease Risk in Chronic Kidney Disease

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Genetic IL-6 Signaling Modifies Incident Coronary Artery Disease Risk in Chronic Kidney Disease

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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