Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity. 1. Introduction Rheumatoid arthritis (RA) is an autoimmune disease, characterized by articular inflammation which can lead to joint destruction. RA prevalence is 1% worldwide with considerable variation between ethnic groups, with a higher prevalence in Caucasians compared with Asiatic populations [1, 2]. This disease is more frequent in females (3？:？1) around the fourth decade ; some studies suggest that sexual hormones, specifically estrogens, can cause hyperactivity in B and T cell functions . RA represents a disease with risk of function disability due to articular damage as a result of ongoing inflammation, which is irretrievable. In order to limit illness incapability, it is necessary to establish the diagnostic as soon as possible and treat the condition. Genetic predisposition for this disease is supported by the following findings: first degree relatives of patients with RA have a four to six times greater risk to develop the disease ; presence of some HLA-DR molecules (HLA-DRB1*0401 and HLA-DRB1*0404) are genetic factors commonly found in RA, and its presence is associated with a more severe disease [6, 7]. The epidemiological genetic information suggests that the heritability for this
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