Interleukin-6 receptor pathways in abdominal aortic aneurysm

SC Harrison, AJP Smith, GT Jones, DI Swerdlow, R Rampuri, MJ Bown, L Folkersen, AF Baas, GJ de Borst, JD Blankensteijn, JF Price, Y (Yolanda) van der Graaf, S McLachlan, O Agu, Bert Hofman, André Uitterlinden, A Franco-Cereceda, YM Ruigrok, F van't Hof, JT PowellAM van Rij, JP Casas, P Eriksson, MV Holmes, FW Asselbergs, AD Hingorani, SE Humphries

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Abstract

We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach. Up to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls [standardized mean difference (SMD) 0.46 SD, 95 CI 0.250.66, I-2 70, P 1.1 105 random effects]. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95 CI: 0.800.89, I-2 0, A Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management.
Original languageUndefined/Unknown
Pages (from-to)3707-3716
Number of pages10
JournalEuropean Heart Journal
Volume34
Issue number48
DOIs
Publication statusPublished - 2013

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