A family based 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 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.
Department of Experimental Pathology, University of Pisa, via Roma 67, I-56126 Pisa, Italy.
L
L
Caponi
E
E
Petit-Teixeira
M
M
Sebbag
F
F
Bongiorni
S
S
Moscato
F
F
Pratesi
C
C
Pierlot
J
J
Osorio
S
S
Chapuy-Regaud
M
M
Guerrin
F
F
Cornelis
G
G
Serre
P
P
Migliorini
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D000080062:Protein-Arginine Deiminase Type 1; D044465:White People
D006867:Hydrolases; D000080062:Protein-Arginine Deiminase Type 1