Abstract
IntroductionA 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.MethodsA 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.ResultsWe 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.ConclusionsUsing 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.
Highlights
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
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
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
Summary
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. In addition to human leucocyte antigen (HLA) [3] – the first identified genetic risk factor – and four other replicated regions – including the protein tyrosine phosphatase N22 gene (PTPN22) [4], the TNF receptorassociated factor 1 gene (TRAF1)/complement component factor 5 (C5) locus [5,6,7], the 6q23 locus near the TNFα-induced protein 3 gene (TNFAIP3) [8,9], and the signal transducer and activator of transcription 4 (STAT4) gene [10,11] – a new genetic region associated with RA was described in the Dutch population [12] This region encompassing KIAA1109/Tenr/IL2/IL21 is contained in a large block (480 kb) of linkage disequilibrium located on chromosome 4q27 and includes the IL2 and IL21 genes, which are both plausible functional candidate loci for RA. The last meta-analysis performed with the North American Rheumatoid Arthritis Consortium, the Epidemiological Investigation of Rheumatoid Arthritis and the Wellcome Trust Case Control Consortium studies, with 3,393 RA patients and 12,462 controls, observed evidence of association of 4q27 with RA in an independent replication, suggesting that 4q27 is a true-positive association [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
