Epistatic interaction between FCRL3 and NFkappaB1 genes in Spanish patients with rheumatoid arthritis.
BACKGROUND
A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor-like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21-23.


OBJECTIVE
To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor kappaB (NFkappaB), a functional polymorphism located in the NFkappaB1 gene was included.


METHODS
734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The -94ins/delATTG NFkappaB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3x2 contingency tables and chi2 values.


RESULTS
No overall differences were found in any of the FCRL3 polymorphisms and in the NFkappaB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFkappaB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFkappaB1 (pc = 0.003).


CONCLUSIONS
The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFkappaB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations.
Immunology Department, Hospital Clinico San Carlos, C/Martín Lagos, s/n, 28040 Madrid, Spain. alfmdoncel@terra.es
A
A
Martínez
E
E
Sánchez
A
A
Valdivia
G
G
Orozco
M A
MA
López-Nevot
D
D
Pascual-Salcedo
A
A
Balsa
B
B
Fernández-Gutiérrez
E G
EG
de la Concha
A
A
García-Sánchez
B P C
BP
Koeleman
E
E
Urcelay
J
J
Martín
D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D013030:Spain
C457775:FCRL3 protein, human; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D011971:Receptors, Immunologic