Genetic association of interleukin-4 VNTR polymorphism with susceptibility to rheumatoid arthritis in South Gujarat population

Abstract

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease, which causes swelling and severe pain within joints. The variable number tandem repeats (VNTR) polymorphism of interleukin-4 (IL4) gene has been associated with autoimmune diseases including RA. The study investigated the association of IL4 VNTR (IVS3; R1 > R2) polymorphism with RA susceptibility in South Gujarat population of India. Polymerase chain reaction (PCR) method was used for genotyping of IL4 VNTR polymorphism in 302 RA patients and 334 controls and ELISA was used for estimation of plasma IL-4 levels. The genotype and allele frequencies of the polymorphism were significantly differed between RA patients and control population (p < 0.0001), suggesting that IL4 VNTR polymorphism is associated with RA susceptibility in South Gujarat population. The susceptible ‘R2’ allele was prevalent in RA group as compared to the control group (79.4% vs 64.00%; p < 0.0001). Moreover, both the genotype and allele frequencies were significantly differed between severe and mild RA patients (p = 0.0039 & p = 0.0005 respectively). The plasma IL-4 levels (p = 0.0216) and genotype-phenotype correlation revealed significant increased IL-4 levels for R2R2 genotype in RA patients compared to controls (p = 0.0265). The IL-4 levels were significantly higher in R2R2 genotype when compared to R1R1 and R1R2 genotypes in RA patients (p = 0.007 & p = 0.03 respectively). Furthermore, IL-4 levels were significantly increased in severe RA patients compared to mild (p = 0.0293). Both, IL-4 levels and R2R2 genotypes were positively correlated with rheumatoid factor (r = 0.49, p = 0.0009 & r = 0.41, p = 0.035 respectively). Overall, the study for the first time suggests that IL4 VNTR R2 allele may be associated with susceptibility to RA in South Gujarat population and it is likely to play a role in increased IL-4 levels thereby contributing to RA pathogenesis.