Objective: A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk.
Methods: In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor β1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens).
Results: Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99-1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects.
Conclusion: A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.
Single nucleotide polymorphism
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Association of a Multigenetic Pro-Inflammatory Profile with Ischaemic Stroke
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Charité - Universitätsmedizin Berlin