The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study.
The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.
Jacq
Laurent
L
GenHotel-EA3886, Evry-Paris VII Universities, 91057 Evry-Genopole cedex, France. laurent@polyarthrite.net
Garnier
Sophie
S
Dieudé
Philippe
P
Michou
Laëtitia
L
Pierlot
Céline
C
Migliorini
Paola
P
Balsa
Alejandro
A
Westhovens
René
R
Barrera
Pilar
P
Alves
Helena
H
Vaz
Carlos
C
Fernandes
Manuela
M
Pascual-Salcedo
Dora
D
Bombardieri
Stefano
S
Dequeker
Jan
J
Radstake
Timothy R
TR
Van Riel
Piet
P
van de Putte
Leo
L
Lopes-Vaz
Antonio
A
Glikmans
Elodie
E
Barbet
Sandra
S
Lasbleiz
Sandra
S
Lemaire
Isabelle
I
Quillet
Patrick
P
Hilliquin
Pascal
P
Teixeira
Vitor Hugo
VH
Petit-Teixeira
Elisabeth
E
Mbarek
Hamdi
H
Prum
Bernard
B
Bardin
Thomas
T
Cornélis
François
F
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005060:Europe / Q000208:ethnology; D005192:Family Health / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D039564:Integrin alphaV