Association of polymorphic variants in IL1B gene with secretion of IL-1β protein and inflammatory markers in north Indian rheumatoid arthritis patients

Publication date: 30 January 2018
Source:Gene, Volume 641
Author(s): Mohd Jahid, Rehan-Ul-Haq, Diwesh Chawla, Rajnish Avasthi, Rafat Sultana Ahmed
The proinflammatory cytokine interleukin-1beta (IL-1β) is a key mediator of inflammation which affects cell proliferation and differentiation. IL-1β is considered to contribute to the pathophysiology of rheumatoid arthritis (RA). Polymorphisms in cytokine genes are highly influenced by ethnicity. Hence, in this study polymorphism of the IL1B-511(C/T) within promoter region was analyzed by using polymerase chain reaction-restriction fragment length Polymorphism (PCR-RFLP) in 187 RA patients and 214 controls. The prevalence of different genotypes and allelic frequency distribution was compared in RA patients and controls. Levels of inflammatory markers and serum levels of IL-1β were estimated by ELISA The serum inflammatory markers levels were significantly higher in RA patients as compared to controls (RF=127.3±21.3U/mL, Anti-CCP=17.8±8.3U/mL, CRP=17.86±7.1mg/L and IL-1β=21.25±4.19pg/mL in RA patients p<0.01). The frequency of heterozygous mutant (C/T) and homozygous mutant (T/T) variants were significantly higher in RA patients as compared to controls and the odds ratios by logistic regression were (OR=2.2, p<0.001) and (OR=3.21, p<0.01) respectively. The association persisted on combining the heterozygous mutant and homozygous mutant (CT+TT) together as compared to controls (OR=2.39; p<0.001). Positive and significant (p<0.05) correlation of circulating IL-1β levels with RF (r=0.232), anti-CCP (r=0.207) and CRP (r=0.166) among RA patients were found. The levels of anti-CCP were significantly higher in homozygous mutant variants (TT) as well as the heterozygous mutant variants (C/T) in comparison to the wild variants (CC) (p<0.01). The results of this study reveal that mutant allele (T) of IL1B-511 promoter SNP tends to be associated with elevated anti-CCP and IL-1β levels as observed in RA patients and hence disease susceptibility.



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