The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for 
lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early 
T-cell activation. An association has recently been reported between the 
PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid 
arthritis (RA), among other autoimmune diseases. Expected linkage proof for 
consistency cannot be definitely produced by an affected sib-pair (ASP) 
analysis. Our aim was therefore to search for linkage evidence with the 
transmission disequilibrium test. DNA from the French Caucasian population was 
available for two samples of 100 families with one RA patient and both parents, 
and for 88 RA index cases from RA ASP families. Genotyping was carried out by 
PCR-restriction fragment length polymorphism. The analysis was performed using 
the transmission disequilibrium test, genotype relative risk and ASP-based 
analysis. The transmission disequilibrium test of the PTPN22-620W allele 
revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). 
The genotype relative risk showed the risk allele in 34% of RF+ RA patients and 
in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, 
odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation 
showed no enriched risk allele in RA multiplex families, resulting in a lack of 
power of ASP analysis, explaining the published negative results. This study is 
the first to show linkage of PTPN22 to RF+ RA, consistent with PTPN22 as a new 
RA gene.