Increased RA susceptibility was significantly associated with the minor alleles of padi4_89 (P = 2.3 x 10(-5)), padi4_90 (P = 2.3 x 10(-5)), padi4_92 (P = 2.1 x 10(-5)), and padi4_104 (P = 1.1 x 10(-3)) and the haplotype carrying the 4 minor alleles (P = 1.0 x 10(-4)).
Our results imply that the PADI4 haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.
Regarding the individual PADI4 variants, padi4_89 (A-->G), padi4_90 (C-->T), and padi4_94 (C-->T) were significantly associated with RA (patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1-2.3).
MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4rs1748033 polymorphisms were a risk factor in codominant and recessive one.
The functional haplotype of peptidylarginine deiminase IV (S55G, A82V and A112G) associated with susceptibility to rheumatoid arthritis dominates apoptosis of acute T leukemia Jurkat cells.
Because most included populations in this meta-analysis were Asian, further studies are needed to elucidate whether the PADI4-104C/T gene confers RA in other ethnic groups.
In stratification analyses, a significantly increased risk for RA associated with the PADI4rs2240340 AA genotype was evident among older patients and patients who were anticitrullinated protein antibody (ACPA)-positive compared with the PADI4rs2240340 GG/GA genotype.
Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intracellular citrullinated proteins and anticitrullinated protein antibodies.
The data presented here show that none of the naturally occurring haplotypes of the PADI4 gene conferred susceptibility to RA in an average group of Hungarian patients; this is in agreement with findings for other European populations.
The results of our group and from the British and French studies strongly suggest that polymorphisms of the PADI4 gene do not play a role in susceptibility to RA in European populations.
It is concluded that PADI4 SNPs, functional haplotype and PADI4 expression may contribute to an inherited predisposition to RA in a Chinese population.
Here, we determine if single nucleotide polymorphism rs2240335 in <i>PADI4</i>, whose G allele is associated with reduced PAD4 in neutrophils, correlates with NETs, anti-histone antibodies, and rheumatoid arthritis susceptibility in North Americans.
This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations.