S2 rulline (AKA). These antibodies are a marker of RA, as they are absent in other disorders. The enzyme responsible for the generation of citrulline residues, peptidylarginine deiminase (PAD), has different isoforms, with a specific tissue distribution. PADV, expressed in monocytes, might be responsible for the deimination of arginine residues of synovial proteins and thus be involved in the generation of epitopes for RA-specific antibodies. The ECRAF genome scan showed suggestive linkage evidence at PADV locus on chromosome1 (P< 0.005). We decided to analyze PAD V as a candidate gene for RA, studying a cohort of 100 RA patients (tested for AKA) and their unaffected parents. Investigation (by single-strand conformation polymorphism [SSCP] analysis and sequencing) of the 16 exons, 5′ and 3′ regions of the PAD V gene provided polymorphisms in the 5′, exons 3, 4, and 7 and 3′ regions. Analysis used the transmission disequilibrium test and the haplotype relative risk for alleles and haplotypes with Analyze and Genhunter2 programs. We found an association between RA and one PAD V haplotype (38% in RA versus 17% in controls)(P< 0.007). The association was also observed in the AKA+ RA subgroup (41%)(P< 0.03). In conclusion, the PAD V gene may be considered one of the genetic factors that confer susceptibility to RA. Studies are in progress to clarify the relationship between the PAD V haplotypes, the enzyme activity and the production of anticitrulline antibodies.