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

Vitor Hugo Teixeira; Celine Pierlot; Paola Migliorini; Alejandro Balsa; René Westhovens; Pilar Barrera; Helena Alves; Carlos Vaz; Manuela Fernandes; Dora Pascual-Salcedo; Stefano Bombardieri; Jan Dequeker; Timothy R Radstake; Piet Van Riel; Leo van de Putte; Antonio Lopes-Vaz; Thomas Bardin; Bernard Prum; François Cornélis; Elisabeth Petit-Teixeira

doi:10.1186/ar2654

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

Vitor Hugo Teixeira, Celine Pierlot, Paola Migliorini, Alejandro Balsa, René Westhovens, Pilar Barrera, Helena Alves, Carlos Vaz, Manuela Fernandes, Dora Pascual-Salcedo, Stefano Bombardieri, Jan Dequeker, Timothy R Radstake, Piet Van Riel, Leo van de Putte, Antonio Lopes-Vaz, Thomas Bardin, Bernard Prum, François Cornélis, Elisabeth Petit-Teixeira

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	R45
Journal	Arthritis Research & Therapy
Volume	11
Issue number	2
DOIs	https://doi.org/10.1186/ar2654
Publication status	Published - 2009
Externally published	Yes

Keywords

Adult
Arthritis, Rheumatoid
Chromosomes, Human, Pair 4
Europe
Family
Female
Genetic Predisposition to Disease
Humans
Interleukin-2
Interleukins
Male
Polymorphism, Single Nucleotide
Journal Article
Research Support, Non-U.S. Gov't

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10.1186/ar2654

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Teixeira, V. H., Pierlot, C., Migliorini, P., Balsa, A., Westhovens, R., Barrera, P., Alves, H., Vaz, C., Fernandes, M., Pascual-Salcedo, D., Bombardieri, S., Dequeker, J., Radstake, T. R., Van Riel, P., van de Putte, L., Lopes-Vaz, A., Bardin, T., Prum, B., Cornélis, F. (2009). Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study. Arthritis Research & Therapy, 11(2), R45. https://doi.org/10.1186/ar2654

@article{835a4ca02f4e4da0b7104e09182512f7,

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

abstract = "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.",

keywords = "Adult, Arthritis, Rheumatoid, Chromosomes, Human, Pair 4, Europe, Family, Female, Genetic Predisposition to Disease, Humans, Interleukin-2, Interleukins, Male, Polymorphism, Single Nucleotide, Journal Article, Research Support, Non-U.S. Gov't",

author = "Teixeira, {Vitor Hugo} and Celine Pierlot and Paola Migliorini and Alejandro Balsa and Ren{\'e} Westhovens and Pilar Barrera and Helena Alves and Carlos Vaz and Manuela Fernandes and Dora Pascual-Salcedo and Stefano Bombardieri and Jan Dequeker and Radstake, {Timothy R} and {Van Riel}, Piet and {van de Putte}, Leo and Antonio Lopes-Vaz and Thomas Bardin and Bernard Prum and Fran{\c c}ois Corn{\'e}lis and Elisabeth Petit-Teixeira",

year = "2009",

doi = "10.1186/ar2654",

language = "English",

volume = "11",

pages = "R45",

journal = "Arthritis Research & Therapy",

issn = "1478-6354",

publisher = "BioMed Central",

number = "2",

}

Teixeira, VH, Pierlot, C, Migliorini, P, Balsa, A, Westhovens, R, Barrera, P, Alves, H, Vaz, C, Fernandes, M, Pascual-Salcedo, D, Bombardieri, S, Dequeker, J, Radstake, TR, Van Riel, P, van de Putte, L, Lopes-Vaz, A, Bardin, T, Prum, B, Cornélis, F, Petit-Teixeira, E 2009, 'Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study', Arthritis Research & Therapy, vol. 11, no. 2, pp. R45. https://doi.org/10.1186/ar2654

TY - JOUR

T1 - Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

AU - Teixeira, Vitor Hugo

AU - Pierlot, Celine

AU - Migliorini, Paola

AU - Balsa, Alejandro

AU - Westhovens, René

AU - Barrera, Pilar

AU - Alves, Helena

AU - Vaz, Carlos

AU - Fernandes, Manuela

AU - Pascual-Salcedo, Dora

AU - Bombardieri, Stefano

AU - Dequeker, Jan

AU - Radstake, Timothy R

AU - Van Riel, Piet

AU - van de Putte, Leo

AU - Lopes-Vaz, Antonio

AU - Bardin, Thomas

AU - Prum, Bernard

AU - Cornélis, François

AU - Petit-Teixeira, Elisabeth

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Adult

KW - Arthritis, Rheumatoid

KW - Chromosomes, Human, Pair 4

KW - Europe

KW - Family

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Interleukin-2

KW - Interleukins

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/ar2654

DO - 10.1186/ar2654

M3 - Article

C2 - 19302705

SN - 1478-6354

VL - 11

SP - R45

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

IS - 2

ER -

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

Abstract

Keywords

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