The Missense Variation Q705K in CIAS1 / NALP3 / NLRP3 Gene and an NLRP1 Haplotype Are Associated With Celiac Disease

OBJECTIVES: Celiac disease (CD) is a multifactorial common disorder with several susceptibility loci. Variations in theNALP1/NLRP1andNALP3/NLRP3genes have been reported to confer risk for several autoimmune conditions. We hypothesized that polymorphisms in these genes, due to their role in innate immunity and inflammatory processes, may affect susceptibility to CD. METHODS: Two single-nucleotide polymorphisms (SNPs) inNLRP1(rs12150220, rs2670660) and two SNPs (rs10754558, rs35829419) inNLRP3genes were genotyped in 504 CD Italian patients and 256 healthy controls. RESULTS: The minor A allele ofNLRP3rs35829419 (Q705K) polymorphism appeared to exert a protective role against the development of CD (P=0.029; odds ratio (OR)=0.56). Moreover, a particularNLRP1haplotype was associated with predisposition to CD (P=0.003; OR=1.38), even more when present in combination with the rs35829419 major C allele (P=0.002; OR=1.42). CONCLUSIONS: We hypothesized that the deregulation ofCIAS1/NALP3/NLRP3andNALP1/NLRP1inflammasomes could have a role in CD pathogenesis.