Peptidylarginine deiminase 4 polymorphisms in association with antibody status in south indian tamil rheumatoid arthritis population

Authors:V Malini , N Shettu
Int J Biol Med Res. 2018; 9(4): 6485-6496  |  PDF File

Abstract

Aim: Peptidylarginine deiminase 4 (PADI4) gene encoding citrullinating enzyme gained momentum after citrulline was reported to be an antigenic determinant, a target of anti-cyclic citrullinated peptide antibody (ACPA) being the most specific serological marker of rheumatoid arthritis (RA). Thus, we explored the relationship between PADI4 polymorphism and anti-CCP and anti-Sa status in RA patients of South Indian Tamil population. Methods: 207 RA patients and 186 healthy subjects were analyzed for rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), anti-Sa, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), diseases activity score 28 (DAS28) and were genotyped for PADI4. Results: Anti-CCP+/anti-Sa+ RA patients illustrated significant ESR, RF, anti-CCP and DAS28 compared to anti-CCP+/anti-Sa- patients (p< 0.05). Severe DAS28 in anti-CCP+/anti-Sa+ patients to anti-CCP positive alone patients (p=0.001), suggests anti-Sa has a propensity towards joint inflammation. Polymorphisms in PADI4_92, PADI4_94 and PADI4_104 demonstrated to be a susceptible risk locus for RA (p<0.05). CCC haplotype proved to be an extremely linked with RA (p=0.0001). Stratification analyses signified high frequency of PADI4_92 genetic variant in anti-Sa positive subgroups (p=0.004). Conclusion: Our findings conclude that PADI4 gene confers susceptibility to RA, especially PADI4_92 polymorphism being a promising candidate gene for anti-Sa positive patients, suggesting a feed-forward loop between PADI4_92 genetic variant, anti-Sa production and inflammation in South Indian Tamil population.