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
UR - http://www.scopus.com/inward/record.url?scp=84887669101&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/ket269
DO - 10.1093/rheumatology/ket269
M3 - Article
C2 - 24046467
AN - SCOPUS:84887669101
SN - 1462-0324
VL - 52
SP - 2168
EP - 2176
JO - Rheumatology
JF - Rheumatology
IS - 12
M1 - ket269
ER -