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The role of interleukin-10 and its gene polymorphisms in the pathogenesis of abdominal aortic aneurysms

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posted on 15.12.2014, 10:31 by Geraint Lloyd
Background: Abdominal aortic aneurysms (AAA) are associated with a cytokine mediated inflammatory response. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that opposes the actions of inflammatory mediators implicated in AAA formation and expansion. The IL-10 gene has a functional guanine (G) / adenine (A) polymorphism at the -1082 position, a cytosine (C) / thyme (T) polymorphism at -819 and a cytosine (C) / adenine (A) polymorphism at -592. The -819 and -592 polymorphisms are linked, and only 3 haplotypes exist. The -1082 A allele and the ATA haplotypes are associated with reduced IL-10 production. The aim of this study was to determine whether there is an association between these gene polymorphisms and the presence or expansion rate of AAA. Methods: A case control study of 390 patients with AAA and 404 patients without an AAA (296 patients were matched 1:1). Blood samples were genotyped for the IL-10 gene polymorphisms with induced heteroduplex genotyping. In 250 patients the IL-10 plasma concentration was measured and in 178 patients AAA expansion rate was calculated. Results: In the matched analysis the -1082 AA genotype and A allele were significantly more prevalent in patients with an AAA, P=0.0009 (Chi-squared test) and P=0.0002 (Fisher's Exact test) respectively. The odds ratio for the A allele being a risk factor for AAA was 1.87 (96% confidence interval, 1.35-2.59). The ATA haplotype was significantly more prevalent in patients with AAA, P=0.0008 (Chi-squared test). IL-10 plasma concentration was not influenced by genotype or presence of an AAA. The polymorphisms studied were not significantly associated with AAA expansion rate. Conclusions: The proposed mechanism is that impaired IL-10 production results in less inhibition of AAA causing inflammatory mediators.

History

Date of award

01/01/2007

Author affiliation

Medicine

Awarding institution

University of Leicester

Qualification level

Doctoral

Qualification name

MD

Language

en

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