Robert J Barry1, Jawaher A Alsalem1, Juliet Faassen2, Philip I Murray3, S John Curnow1, Graham R Wallace1. 1. Centre for Translational Inflammation Research, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK Academic Unit of Ophthalmology, University of Birmingham, Birmingham and Midland Eye Centre, City Hospital, Birmingham, UK. 2. Centre for Translational Inflammation Research, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK. 3. Centre for Translational Inflammation Research, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK Academic Unit of Ophthalmology, University of Birmingham, Birmingham and Midland Eye Centre, City Hospital, Birmingham, UK Behçet's Centre of Excellence, City Hospital, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK.
Abstract
BACKGROUND: Transforming growth factor β (TGFβ) is an important immunoregulatory cytokine in regulatory T cell (Treg) and Th17-mediated pathology, including uveitis due to Behçet's disease (BD). Of the three isoforms, TGFβ2 is found at highest levels in the aqueous humour of uninflamed eyes. TGFβ signals through a cell-surface receptor comprising three subunits (TGFBR1, 2 and 3). TGFBR3 is considered necessary for TGFβ2 signal transduction, but not for other isoforms. A polymorphism in TGFBR3 (rs1805110) has previously been identified in Han Chinese patients with BD. We investigated the frequency of this polymorphism in a Caucasian population with BD and idiopathic intermediate uveitis (IIU). METHODS: The single-nucleotide polymorphism (SNP) rs1805110 in TGFBR3 was genotyped in 75 BD patients, 92 IIU disease controls and 85 disease-free controls. The association with both diseases was analysed using Fisher's exact test. RESULTS: No significant difference in rs1805110 allele or genotype frequency was observed. A low frequency of the T allele was observed (5.88% control, 9.33% BD, 10.33% IIU) with the TT genotype absent in patients with BD and IIU (1.18% control, 0% BD and 0% IIU). Stratification analysis according to clinical features of BD did not associate with the tested SNP. CONCLUSIONS: RS1805110 is not associated with BD or IIU in Caucasian patients. The T allele frequency is consistent with that presented for Caucasian populations in the HapMap database (p>0.05). Our results differ from the previous analysis in Han Chinese patients (p<0.0001), however, the possibility of having a much smaller effect due to the low minority frequency cannot be excluded. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND: Transforming growth factor β (TGFβ) is an important immunoregulatory cytokine in regulatory T cell (Treg) and Th17-mediated pathology, including uveitis due to Behçet's disease (BD). Of the three isoforms, TGFβ2 is found at highest levels in the aqueous humour of uninflamed eyes. TGFβ signals through a cell-surface receptor comprising three subunits (TGFBR1, 2 and 3). TGFBR3 is considered necessary for TGFβ2 signal transduction, but not for other isoforms. A polymorphism in TGFBR3 (rs1805110) has previously been identified in Han Chinese patients with BD. We investigated the frequency of this polymorphism in a Caucasian population with BD and idiopathic intermediate uveitis (IIU). METHODS: The single-nucleotide polymorphism (SNP) rs1805110 in TGFBR3 was genotyped in 75 BD patients, 92 IIU disease controls and 85 disease-free controls. The association with both diseases was analysed using Fisher's exact test. RESULTS: No significant difference in rs1805110 allele or genotype frequency was observed. A low frequency of the T allele was observed (5.88% control, 9.33% BD, 10.33% IIU) with the TT genotype absent in patients with BD and IIU (1.18% control, 0% BD and 0% IIU). Stratification analysis according to clinical features of BD did not associate with the tested SNP. CONCLUSIONS:RS1805110 is not associated with BD or IIU in Caucasian patients. The T allele frequency is consistent with that presented for Caucasian populations in the HapMap database (p>0.05). Our results differ from the previous analysis in Han Chinese patients (p<0.0001), however, the possibility of having a much smaller effect due to the low minority frequency cannot be excluded. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.