Testing for the Association of the KIAA1109/Tenr/IL2/IL21 Gene Region with Rheumatoid Arthritis in a European Family-Based Study
Vitor Hugo Teixeira
(1, 2)
,
Céline Pierlot
(3, 1)
,
Paola Migliorini
(4)
,
Alejandro Balsa
(5)
,
René Westhovens
(6)
,
Pilar Barrera
(7)
,
Helena Alves
(8)
,
Carlos Vaz
(8)
,
Manuela Fernandes
(9, 8)
,
Dora Pascual-Salcedo
(5)
,
Stefano Bombardieri
(4)
,
Jan Dequeker
(10)
,
Timothy R Radstake
(11)
,
Piet van Riel
(11)
,
Leo van De Putte
(11)
,
Antonio Lopes-Vaz
(8)
,
Thomas Bardin
(12)
,
Bernard Prum
(13)
,
François Cornélis
(1)
,
Elisabeth Petit-Teixeira
(1)
1
GenHotel -
Laboratoire de recherche européen pour la polyarthrite rhumatoïde
2 Universidade de Coimbra [Coimbra]
3 UMR CNRS 8009 - Laboratoire de Chimie Organique et Macromoleculaire
4 University of Pisa - Università di Pisa
5 Hospital Universitario La Paz
6 University Hospitals Leuven [Leuven]
7 Nijmegen Medical Centre [Nijmegen]
8 Hospital de São João [Porto]
9 CICECO - Center for Research in Ceramic and Composite Materials
10 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
11 Radboud University [Nijmegen]
12 Service de Rhumatologie [CHU Lariboisière]
13 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
2 Universidade de Coimbra [Coimbra]
3 UMR CNRS 8009 - Laboratoire de Chimie Organique et Macromoleculaire
4 University of Pisa - Università di Pisa
5 Hospital Universitario La Paz
6 University Hospitals Leuven [Leuven]
7 Nijmegen Medical Centre [Nijmegen]
8 Hospital de São João [Porto]
9 CICECO - Center for Research in Ceramic and Composite Materials
10 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
11 Radboud University [Nijmegen]
12 Service de Rhumatologie [CHU Lariboisière]
13 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
René Westhovens
- Fonction : Auteur
- PersonId : 791336
- ORCID : 0000-0002-3432-3073
Thomas Bardin
- Fonction : Auteur
- PersonId : 756614
- ORCID : 0000-0002-5080-4790
Bernard Prum
- Fonction : Auteur
- PersonId : 899353
Elisabeth Petit-Teixeira
- Fonction : Auteur
- PersonId : 172206
- IdHAL : elisabeth-teixeira
- ORCID : 0000-0001-9724-3575
- IdRef : 147506638
Résumé
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. © 2009 Teixeira et al.; licensee BioMed Central Ltd.
Domaines
Génétique humaineFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Testing for the Association of the KIAA1109/Tenr/IL2/IL21 Gene Region with Rheumatoid Arthritis in a European Family-Based Study
|
Résumé |
en
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. © 2009 Teixeira et al.; licensee BioMed Central Ltd.
|
Auteur(s) |
Vitor Hugo Teixeira
1, 2
, Céline Pierlot
3, 1
, Paola Migliorini
4
, Alejandro Balsa
5
, René Westhovens
6
, Pilar Barrera
7
, Helena Alves
8
, Carlos Vaz
8
, Manuela Fernandes
9, 8
, Dora Pascual-Salcedo
5
, Stefano Bombardieri
4
, Jan Dequeker
10
, Timothy R Radstake
11
, Piet van Riel
11
, Leo van De Putte
11
, Antonio Lopes-Vaz
8
, Thomas Bardin
12
, Bernard Prum
13
, François Cornélis
1
, Elisabeth Petit-Teixeira
1
1
GenHotel -
Laboratoire de recherche européen pour la polyarthrite rhumatoïde
( 1061669 )
- 2 rue Gaston Crémieux, CP5727, 91057 EVRY-GENOPOLE cedex
- France
2
Universidade de Coimbra [Coimbra]
( 300707 )
- Palácio dos Grilos
Rua da Ilha
3000-214 Coimbra
- Portugal
3
UMR CNRS 8009 -
Laboratoire de Chimie Organique et Macromoleculaire
( 20668 )
- Universite des Sciences et Technologies, B.P. 90108, 59652, Villeneuve d'Ascq cedex, France
- France
4
University of Pisa - Università di Pisa
( 366408 )
- Lungarno Pacinotti 43 - 56126 Pisa
- Italie
5
Hospital Universitario La Paz
( 1064290 )
- P° de la Castellana, 261
Madrid 28046
- Espagne
6
University Hospitals Leuven [Leuven]
( 327452 )
- Herestraat 49, 3000 Leuven
- Belgique
7
Nijmegen Medical Centre [Nijmegen]
( 347499 )
- Geert Grooteplein Zuid 6525, 6525 GA Nijmegen
- Pays-Bas
8
Hospital de São João [Porto]
( 347026 )
- Alameda Prof. Hernâni Monteiro
4200–319 Porto
- Portugal
9
CICECO -
Center for Research in Ceramic and Composite Materials
( 53123 )
- Department of Ceramics and Glass Engineering 3810-193 Aveiro
- Portugal
10
KU Leuven -
Catholic University of Leuven = Katholieke Universiteit Leuven
( 300656 )
- Oude Markt 13 - bus 5005, 3000 Leuven
- Belgique
11
Radboud University [Nijmegen]
( 300856 )
- Houtlaan 4,
6525 XZ Nijmegen
- Pays-Bas
12
Service de Rhumatologie [CHU Lariboisière]
( 458984 )
- France
13
LBBE -
Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
( 10025 )
- 43 Bld du 11 Novembre 1918 69622 VILLEURBANNE CEDEX
- France
|
Date de publication |
2009
|
Audience |
Internationale
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Langue du document |
Anglais
|
Volume |
11
|
Numéro |
2
|
Domaine(s) |
|
Voir aussi |
|
Mots-clés |
en
Rheumatoid Arthritis Patient, Wellcome Trust Case Control Consortium, Genotype Relative Risk
|
DOI | 10.1186/ar2654 |
PubMed Central | PMC2688193 |
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