The role of IL-1β C-511T as a modifier polymorphism in Cryopyrin-Associated Periodic Syndromes

INTRODUCTION: Cryopyrin-Associated Periodic Syndromes are a subgroup of the Periodic fever syndromes, caused by mutations in the NLRP3 gene. NLRP3 gene mutations can cause 3 clinically different phenotypes. It is known that even the same mutations in the NLRP3 gene can cause different phenotypes. To investigate this situation, we have built a hypothesis that if an individual with IL-1β-511 T/T genotype which is associated with overexpressed IL-1β levels, he/she might have a more severe CAPS phenotype.
METHODS: Thirty-six NLRP3 Exon 3 variant-positive patients with detailed clinical data and 30 healthy controls were selected for the IL-1β genotype investigation. For the analysis of IL-1β -511 allele, the SNP rs1143634 was genotyped using the TaqMan 5'-exonuclease allelic discrimination assay.
RESULTS: Both the Muckle Wells Syndrome patients (severe phenotype) with p.Val198Met mutation and symptomatic patients with p.Gln703Lys variant, did not show an increased IL-1β-511T/T genotype frequency.
DISCUSSION AND CONCLUSION: We suggest that IL-1β-511 T/T polymorphism is not a modifying factor regarding the clinical severity of CAPS patients. However, to expand this theory and in order to find other modifying genetic factors, other polymorphisms of IL-1β or other genes in inflammasome pathway such as Caspase-1 or ASC should be analyzed.