Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

被引:27
|
作者
Teixeira, Vitor Hugo [2 ]
Pierlot, Celine
Migliorini, Paola [3 ]
Balsa, Alejandro [5 ]
Westhovens, Rene [4 ]
Barrera, Pilar [6 ]
Alves, Helena [7 ]
Vaz, Carlos [7 ]
Fernandes, Manuela [7 ]
Pascual-Salcedo, Dora [5 ]
Bombardieri, Stefano [3 ]
Dequeker, Jan [4 ]
Radstake, Timothy R. [6 ]
Van Riel, Piet [6 ]
van de Putte, Leo [6 ]
Lopes-Vaz, Antonio [7 ]
Bardin, Thomas
Prum, Bernard [8 ]
Cornelis, Francois [1 ,9 ,10 ]
Petit-Teixeira, Elisabeth [1 ]
机构
[1] Evry Univ Paris 7, GenHotel EA3886, Univ Med Sch, F-91057 Evry, France
[2] Univ Coimbra, Fac Med, P-3004504 Coimbra, Portugal
[3] Univ Pisa, I-56126 Pisa, Italy
[4] Katholieke Univ Leuven, BE-3000 Louvain, Belgium
[5] Hosp La Paz, Madrid 28046, Spain
[6] Univ Nijmegen, NL-6500 HB Nijmegen, Netherlands
[7] Porto San Joao Hosp, P-4200 Oporto, Portugal
[8] Lab Stat & Genome, F-91000 Evry, France
[9] Lariboisiere Hosp, Assistance Publ Hop Paris, Clin Genet Unit, Pole Lab Imagerie Pharm, F-75010 Paris, France
[10] Ctr Hosp Sud Francilien, Adult Genet Unit, F-91106 Corbeil Essonnes, France
关键词
GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RISK LOCUS; INTERLEUKIN-21; POPULATION; DISEASES; 6Q23;
D O I
10.1186/ar2654
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction 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.
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页数:7
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