No Evidence of Association between Common Autoimmunity STAT4 and IL23R Risk Polymorphisms and Non-Anterior Uveitis

María Carmen Cénit,Marina Begoña Gorroño-Echebarría,Ana Márquez,Javier Martín,María José Del Rio,Esperanza Pato,Joaquín Cañal,David Díaz Valle,Alejandro Fonollosa,Miguel Cordero-Coma,Enrique De Ramón,José Luis García Serrano,Ricardo Blanco,Agustín Martínez-Berriotxoa,Norberto Ortego-Centeno,Manuel Díaz-Llopis,José Manuel Martín-Villa,Alfredo Adán,Blanca Molins

doi:10.1371/journal.pone.0072892

Abstract

ObjectiveSTAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes.MethodsFour functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. ResultsNo statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). ConclusionOur results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.

Highlights

Uveitis can be defined as any inflammation affecting the uveal tract, the middle vascular layer of the eye, in the clinical practice this term includes any intraocular inflammatory process [1]
No large-scale genome-wide association studies in uveitis have been published to date, and only few genetic studies, focused mainly on anterior uveitis, have been conducted to identify the uveitis genetic component [9,10,11]
Only some HLA alleles have been strongly associated with uveitis predisposition [5,6,7,8], and genetic factors outside HLA region influencing uveitis susceptibility remain unknown

Summary

Introduction

Uveitis can be defined as any inflammation affecting the uveal tract, the middle vascular layer of the eye, in the clinical practice this term includes any intraocular inflammatory process [1]. The effect of these alleles just explains a small part of the uveitis heritability and different studies have recently highlighted the implication of non-HLA genetic factors in the susceptibility to this condition [9,10,11]. Different studies have identified IL23R as a susceptibility factor associated to multiple inflammatory conditions [16,17,18]. In these studies several independent signals located within IL23R locus were suggested; only the R381Q (rs11209026) polymorphism, whose minor allele plays a protective role for several autoimmune disease, appear to have a functional involvement [19,20].

Methods

Results

Discussion