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

• Published in: Annals of the rheumatic diseases Vol. 64; no. 4; pp. 587 - 593
• Main Authors: Caponi, L, Petit-Teixeira, E, Sebbag, M, Bongiorni, F, Moscato, S, Pratesi, F, Pierlot, C, Osorio, J, Chapuy-Regaud, S, Guerrin, M, Cornelis, F, Serre, G, Migliorini, P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.04.2005; BMJ; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: ACPA; Adult; AhFibA; anti-citrullinated protein antibodies; anti-human fibrin(ogen) autoantibodies; Arthritis, Rheumatoid - ethnology; Arthritis, Rheumatoid - genetics; Biological and medical sciences; CCP; Cloning; Consortia; cyclic citrullinated peptides; Disease; disease susceptibility; Diseases of the osteoarticular system; ECRAF; Enzymes; European Consortium for Rheumatoid Arthritis Families; European Continental Ancestry Group; Extended Report; Families & family life; Female; Gene Frequency; Genes; Genetic Predisposition to Disease; Genetics; Genomes; genotype relative risk; GRR; Haplotypes; Human genetics; Human health and pathology; Humans; Hydrolases - genetics; Hypotheses; Inflammatory joint diseases; Life Sciences; Male; Medical sciences; Middle Aged; PAD; Pathogenesis; peptidylarginine deiminase; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; Population; Proteins; restriction fragment length polymorphism; RFLP; Rheumatism; Rheumatoid arthritis; rheumatoid factor; Rheumatology; Rhumatology and musculoskeletal system; single nucleotide polymorphism; single strand conformational polymorphism; SNP; SSCP; TDT; transmission disequilibrium test; France; Europe; Chronic; French; Gene; Family study; Rheumatoid arthritis; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Haplotypes; Rheumatoid; Genetic Predisposition to Disease; Gene Frequency; Humans; Middle Aged; Restriction Fragment Length; Male; European Continental Ancestry Group; Single-Stranded Conformational; Arthritis; Hydrolases; Adult; Female; Polymorphism
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2004.026831

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 PADI4 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 PADI4 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 PADI4 gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and haplotypes 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 PADI4 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.