A family base study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population

Background: Autoantibodies to citrullinated proteins (ACPA) are considered a specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the enzyme that converts arginyl into citrullyl residues; different isoforms of the enzyme are expressed in mammals. it has been suggested that the PAD14 gene may contribute to genetic susceptibility to rheumatoid arthritis, but conflicting results have been obtained in different populations. Objective: To test the hypothesis that the PAD14 gene may confer susceptibility to rheumatoid arthritis in a white French population, using powerful and highly reliable family based association tests. Methods: DNA samples were analysed from 100 families where one member was affected by rheumatoid arthritis and both parents were available for sampling. Five single nucleotide polymorphisms, located within the PAD14 gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and kaplotypes were constructed. The analysis involved use of the transmission disequilibrium test and genotype relative risk. ACPA were detected by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen. Results: No single SNP or haplotype was associated with the disease, or was preferentially transmitted. No association was found when patients were partitioned according to ACPA positivity. Conclusions: No PAD14 haplotype is associated with rheumatoid arthritis in a white French population. The role of genes encoding the other PAD isoforms, or modulating tissue expression or enzyme activity, remains to be elucidated.