Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study.
BACKGROUND
A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach.


METHODS
A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk.


RESULTS
We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients.


CONCLUSIONS
Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association.
Teixeira
Vitor Hugo
VH
GenHotel-EA3886, Evry University - Paris 7 University Medical School, AutoCure European Consortium, Evry-Genopole, France. vitor@polyarthrite.net
Pierlot
Celine
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
Bardin
Thomas
T
Prum
Bernard
B
Cornélis
François
F
Petit-Teixeira
Elisabeth
E
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005060:Europe; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000098546:Interleukin-21
C508594:IL2 protein, human; D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21