Protective effect of an ERAP1 haplotype in ankylosing spondylitis

Investigating non-MHC genes in HLA-B27-positive individuals

Bruno Filipe Bettencourt, Fabiana Leal Rocha, Helena Alves, Rosa Amorim, Joana Caetano-Lopes, Elsa Vieira-Sousa, Fernando Pimentel-Santos, Manuela Lima, Graça Porto, Jaime C. Branco, João Eurico Fonseca, Jácome Bruges-Armas

Research output: Contribution to journalArticle

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Abstract

Objective. The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.Methods. A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).Results. ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10-3] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10-2), rs10050860 (OR = 0.7, P = 2.3 × 10-2), rs2287987 (OR = 0.6, P = 1.3 × 10-2). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10-3) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10-2). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10-2, OR = 1.3). No associations were observed in the TNFSF15 region.Conclusion. The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.

Original languageEnglish
Article numberket269
Pages (from-to)2168-2176
Number of pages9
JournalRheumatology (United Kingdom)
Volume52
Issue number12
DOIs
Publication statusPublished - 1 Dec 2013

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HLA-B27 Antigen
Ankylosing Spondylitis
Haplotypes
Single Nucleotide Polymorphism
Odds Ratio
Genes
Healthy Volunteers

Keywords

  • Ankylosing spondylitis
  • ERAP1
  • IL23R
  • Protection haplotype
  • TNFSF15

Cite this

Bettencourt, Bruno Filipe ; Rocha, Fabiana Leal ; Alves, Helena ; Amorim, Rosa ; Caetano-Lopes, Joana ; Vieira-Sousa, Elsa ; Pimentel-Santos, Fernando ; Lima, Manuela ; Porto, Graça ; Branco, Jaime C. ; Fonseca, João Eurico ; Bruges-Armas, Jácome. / Protective effect of an ERAP1 haplotype in ankylosing spondylitis : Investigating non-MHC genes in HLA-B27-positive individuals. In: Rheumatology (United Kingdom). 2013 ; Vol. 52, No. 12. pp. 2168-2176.
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title = "Protective effect of an ERAP1 haplotype in ankylosing spondylitis: Investigating non-MHC genes in HLA-B27-positive individuals",
abstract = "Objective. The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.Methods. A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).Results. ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10-3] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10-2), rs10050860 (OR = 0.7, P = 2.3 × 10-2), rs2287987 (OR = 0.6, P = 1.3 × 10-2). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10-3) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10-2). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10-2, OR = 1.3). No associations were observed in the TNFSF15 region.Conclusion. The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.",
keywords = "Ankylosing spondylitis, ERAP1, IL23R, Protection haplotype, TNFSF15",
author = "Bettencourt, {Bruno Filipe} and Rocha, {Fabiana Leal} and Helena Alves and Rosa Amorim and Joana Caetano-Lopes and Elsa Vieira-Sousa and Fernando Pimentel-Santos and Manuela Lima and Gra{\cc}a Porto and Branco, {Jaime C.} and Fonseca, {Jo{\~a}o Eurico} and J{\'a}come Bruges-Armas",
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Bettencourt, BF, Rocha, FL, Alves, H, Amorim, R, Caetano-Lopes, J, Vieira-Sousa, E, Pimentel-Santos, F, Lima, M, Porto, G, Branco, JC, Fonseca, JE & Bruges-Armas, J 2013, 'Protective effect of an ERAP1 haplotype in ankylosing spondylitis: Investigating non-MHC genes in HLA-B27-positive individuals', Rheumatology (United Kingdom), vol. 52, no. 12, ket269, pp. 2168-2176. https://doi.org/10.1093/rheumatology/ket269

Protective effect of an ERAP1 haplotype in ankylosing spondylitis : Investigating non-MHC genes in HLA-B27-positive individuals. / Bettencourt, Bruno Filipe; Rocha, Fabiana Leal; Alves, Helena; Amorim, Rosa; Caetano-Lopes, Joana; Vieira-Sousa, Elsa; Pimentel-Santos, Fernando; Lima, Manuela; Porto, Graça; Branco, Jaime C.; Fonseca, João Eurico; Bruges-Armas, Jácome.

In: Rheumatology (United Kingdom), Vol. 52, No. 12, ket269, 01.12.2013, p. 2168-2176.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protective effect of an ERAP1 haplotype in ankylosing spondylitis

T2 - Investigating non-MHC genes in HLA-B27-positive individuals

AU - Bettencourt, Bruno Filipe

AU - Rocha, Fabiana Leal

AU - Alves, Helena

AU - Amorim, Rosa

AU - Caetano-Lopes, Joana

AU - Vieira-Sousa, Elsa

AU - Pimentel-Santos, Fernando

AU - Lima, Manuela

AU - Porto, Graça

AU - Branco, Jaime C.

AU - Fonseca, João Eurico

AU - Bruges-Armas, Jácome

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Objective. The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.Methods. A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).Results. ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10-3] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10-2), rs10050860 (OR = 0.7, P = 2.3 × 10-2), rs2287987 (OR = 0.6, P = 1.3 × 10-2). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10-3) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10-2). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10-2, OR = 1.3). No associations were observed in the TNFSF15 region.Conclusion. The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.

AB - Objective. The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.Methods. A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).Results. ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10-3] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10-2), rs10050860 (OR = 0.7, P = 2.3 × 10-2), rs2287987 (OR = 0.6, P = 1.3 × 10-2). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10-3) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10-2). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10-2, OR = 1.3). No associations were observed in the TNFSF15 region.Conclusion. The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.

KW - Ankylosing spondylitis

KW - ERAP1

KW - IL23R

KW - Protection haplotype

KW - TNFSF15

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U2 - 10.1093/rheumatology/ket269

DO - 10.1093/rheumatology/ket269

M3 - Article

VL - 52

SP - 2168

EP - 2176

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 12

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