TY - JOUR
T1 - Specific association of IL17A genetic variants with panuveitis
AU - Mucientes, Arkaitz
AU - Márquez, Ana
AU - Cordero-Coma, Miguel
AU - Martín-Villa, José Manuel
AU - Gorroño-Echebarría, Marina Begoña
AU - Blanco, Ricardo
AU - Valle, David Díaz
AU - Benítez-Del-Castillo, José Manuel
AU - José Del Rio, María
AU - Blanco, Ana
AU - Olea, Jose Luis
AU - Cordero, Yolanda
AU - Capella, María José
AU - Gonzalez, Jacobo
AU - Díaz-Llopis, Manuel
AU - Ortego-Centeno, Norberto
AU - Adán, Alfredo
AU - Ruiz-Arruza, Ioana
AU - Llorenç, Víctor
AU - Fonollosa, Alejandro
AU - Martín, Javier
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Background/aims A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to nonanterior uveitis and its main clinical subgroups. Methods Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls. Results The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis. Conclusions Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology. Subtitle Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.
AB - Background/aims A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to nonanterior uveitis and its main clinical subgroups. Methods Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls. Results The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis. Conclusions Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology. Subtitle Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.
U2 - 10.1136/bjophthalmol-2014-306106
DO - 10.1136/bjophthalmol-2014-306106
M3 - Article
VL - 99
SP - 566
EP - 570
JO - British Journal of Ophthalmology
JF - British Journal of Ophthalmology
SN - 0007-1161
IS - 4
ER -