P11 Genetics behind the systemic inflammation in psoriasis: functional aspects of NLRP3 polymorphisms

Abstract The systemic inflammation in psoriasis is thought to underlie the high prevalence of cardiovascular comorbidity, but the underlying mechanisms are poorly understood. The NLRP3 inflammasome is strongly linked to cardiovascular disease (CVD) and is genetically associated with both CVD and psoriasis. In this study, we investigated the association of two single nucleotide polymorphisms (SNPs) in the NLRP3 gene (rs10754555 and rs12239046) with psoriasis. These SNPs are associated with systemic inflammation and rs10754555 is strongly linked with cardiovascular risk and mortality. DNA from 491 families comprising 1988 individuals were genotyped and analysed using a family-based association test. A significant association of rs12239046 [odds ratio (OR): 1.29; P = 0.018] and a marginally significant association of rs10754555 (OR: 1.24; P = 0.054) with psoriasis susceptibility was identified. Further, using flow cytometry, we found that monocytes from individuals heterozygous for rs10754555, express significantly more NLRP3 when stimulated with LPS for 60 min compared with the wild type. SNP rs12239046 did not exhibit this phenomenon. Intriguingly, the psoriasis patients homozygous for the rs10754555 risk allele were on anti-TNFα-treatment, proposing a more severe phenotype. Our results suggest a genetic component contributing to the systemic inflammation in psoriasis patients. This genetic insight could potentially be used to identify psoriasis patients at higher risk of systemic inflammation and cardiovascular complications.