Promoter polymorphisms of neuropeptide Y, interleukin-1B and increased IL-1β levels are associated with rheumatoid arthritis susceptibility in South Gujarat population

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction. Interleukin-1B(IL-1β) has been implicated in RA, and neuropeptide Y (NPY) induces the release of pro-inflammatory cytokines including IL1-β, TNF-α and IL-6. Single nucleotide polymorphisms (SNPs) in NPY and IL1B gene may lead to their altered levels leading to RA pathogenesis. Therefore, we aimed to investigate association of NPY rs16147(T > C) SNP, and genotype–phenotype correlation of the IL1B rs16944(C > T) SNP in 302 RA patients and 337 controls by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Both the genotype and allele frequencies for NPY rs16147(T > C)(p = 0.0019 &p = 0.012) and IL1B rs16944(C > T)(p = 0.0024 &p = 0.0014) SNPs differed significantly between RA patients and controls. The odds ratios of 1.23 and 1.47 for NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs respectively, suggest that these SNPs may be genetic risk factor for RA in South Gujarat population. The plasma IL-1β levels(p = 0.0332) and genotype-phenotype correlation of IL1B rs16944(C > T) SNP suggested increased IL-1β levels, particularly in patients with susceptible ‘TT' genotypes(p < 0.0001). Additionally, plasma IL-1β level was significantly increased in severe RA patients (p = 0.0025) and positively correlated with Rheumatoid factor(RF) (r = 0.9240, p < 0.0001), suggesting the role of IL-1β in disease severity. Overall, the study for the first time suggests that NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs may be associated with RA susceptibility in South Gujarat population. Additionally, the IL1B rs16944 susceptible ‘TT' genotype may lead to increased IL-1β levels, thereby contributing to RA pathogenesis and severity.