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New insights into the genetic component of non-infectious uveitis through an Immunochip strategy

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Marquez, A
  • Cordero-Coma, M
  • Martin-Villa, JM
  • Gorroño-Echebarría MB
  • Blanco, R
  • Díaz Valle D
  • del Rio, MJ
  • Blanco, A
  • Olea, JL
  • Cordero, Y
  • Capella, MJ
  • Ortego-Centeno, N
  • Ruiz-Arruza, I
  • Llorenc, V
  • Adan, A
  • Fonollosa, A
  • ten Berge, J
  • Atan, D
  • Dick, AD
  • De Boer, JH
  • Kuiper, J
  • Rothova, A
  • Martin, J

Abstract

Background Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. Methods 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with noninfectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. Results The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLAA* 2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. Conclusions We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

Datos de la publicación

ISSN/ISSNe:
0022-2593, 1468-6244

JOURNAL OF MEDICAL GENETICS  BMJ PUBLISHING GROUP

Tipo:
Article
Páginas:
38-46
Factor de Impacto:
3,304 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 11

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Keywords

  • *Immunochip; *human leukocyte antigen; *meta-analysis; *non-anterior uveitis; *non-infectious uveitis

Proyectos asociados

ESTUDIO CONTROLADO FRENTE A PLACEBO, ALEATORIZADO, DOBLE ENMASCARADO, DE EFICACIA DE GEVOKIZUMAB EN EL TRATAMIENTO DE PACIENTES CON UVEITIS POR ENFERMEDAD DE BEHÇET.

Investigador Principal: MANUEL DÍAZ LLOPIS

CL3-78989-002

ESTUDIO OBSERVACIONAL Y RETROSPECTIVO PARA CONOCER EL IMPACTO Y POSTERIOR RECUPERACIÓN EN AGUDEZA VISUAL Y CARACTERÍSTICAS ANATÓMICAS POR OCT, EN PACIENTES CON DEGENERACIÓN MACULAR ASOCIADA A LA EDAD EXUDATIVA Y TRATADOS CON RANIBIZUMAB DE FORMA REACTIVA (PRN).

Investigador Principal: MANUEL DÍAZ LLOPIS

BAY-RAN-2012-01

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Investigador Principal: ROBERTO GALLEGO PINAZO

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ESTUDIO PROSPECTIVO Y ABIERTO EN CENTRO ÚNICO PARA EVALUAR LOS PATRONES DE PRESIÓN INTRAOCULAR MEDIANTE SENSIMED TRIGGERFISH AL RECIBIR UNA INYECCIÓN ANTI-VEGF.

Investigador Principal: ROBERTO GALLEGO PINAZO

TF-1304

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