Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility.
OBJECTIVE
To examine the expression level and function of follistatin-related protein gene (FRP, also referred to as FSTL1) in rheumatoid arthritis (RA), and possible association of its polymorphisms with genetic susceptibility to RA.


METHODS
FRP mRNA expression levels in the synovial tissues from 10 patients with RA and 5 patients with OA were measured using real-time RT-PCR. Effects on the growth of synovial cells were evaluated by stably introducing FRP cDNA into a rheumatoid synovial cell line, E11. Screening of genomic DNA variations was done using DNA from 12 patients with RA and 12 healthy individuals by direct sequencing. Genotypes at the detected polymorphic sites were determined in 224 patients with RA and 220 healthy individuals using PCR-single strand conformation polymorphism.


RESULTS
FRP mRNA was overexpressed in synovial tissues from RA patients by 2.3-fold as compared with those from OA. A rheumatoid synovial cell line (E11) transfected with FRP exhibited reduced proliferation, probably mediated by secreted FRP molecule. 16 genomic variations were identified, among which 4 were polymorphisms within the promoter region and exons, and the remainder were either rare variations or intronic polymorphisms. Genotyping of 4 polymorphic sites did not reveal statistically significant association with the susceptibility to RA.


CONCLUSIONS
FRP mRNA is overexpressed in RA synovium, the product of which exerts inhibitory activity on synovial cell growth. Although new polymorphic sites were identified, they were not associated with susceptibility to RA, suggesting that overexpression of FRP is secondarily caused by synovial environment of RA.
Ehara
Y
Y
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Sakurai
D
D
Tsuchiya
N
N
Nakano
K
K
Tanaka
Y
Y
Yamaguchi
A
A
Tokunaga
K
K
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005260:Female; D038702:Follistatin-Related Proteins / Q000235:genetics*; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000502:physiology*; D014162:Transfection
D038702:Follistatin-Related Proteins; D012333:RNA, Messenger; C448799:FSTL1 protein, human