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Robert John Barry, Jawaher Alsalem, Graham R Wallace, Philip Ian Murray, John Curnow; Association analysis of TGFBR3 gene with Behcet’s Disease and Idiopathic Intermediate Uveitis in a Caucasian population. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6420.
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© ARVO (1962-2015); The Authors (2016-present)
Transforming Growth Factor-β (TGFβ) is an important immunoregulatory cytokine in uveitis. In experimental models, TGFβ has been shown to drive differentiation of naïve CD4+ T-cells to a pathogenic Th17 phenotype in the presence of pro-inflammatory co-stimulatory molecules. TGFβ exists in three isoforms and signals through a cell-surface receptor comprising three subunits. Of these isoforms, TGFβ2 predominates in aqueous humour and is believed to require the TGFBR3 receptor subunit in addition to TGFBR1/2. A polymorphism in TGFBR3 (rs1805110) has previously been identified in Chinese Han patients with Behcet’s Disease (BD). We wished to investigate the frequency of this polymorphism in a population of Caucasian patients with BD, with a comparison to a population of Caucasian patients with idiopathic intermediate uveitis (IIU).
The single-nucleotide polymorphism (SNP) rs1805110 in TGFBR3 was genotyped in 75 patients with BD, 72 with IIU and 88 healthy controls using a polymerase chain reaction restriction length polymorphism assay. The association of this SNP with both diseases was analysed using Fisher’s exact test.
An increased frequency of the rs1805110 T allele was observed in both BD patients and IIU patients as compared to healthy controls (T allele frequency 37.33%, 26.39% and 7.39% respectively). A statistically significant increased frequency of the rs1805110 TT genotype was observed in both BD patients (p<0.0001, odds ratio = 43.50, 95% confidence interval 5.72-331), and IIU patients (p<0.0001, odds ratio = 22.89, 95% confidence interval 2.94-178.20) as compared to healthy controls. Stratification analysis according to clinical features of BD did not associate with the tested SNP.
Our results suggest the prevalence of the rs1805110 T allele and TT genotype is increased in both BD and IIU patients from Caucasian populations as compared to healthy controls. These findings are consistent with those previously observed in Chinese Han patients with BD, suggesting a potential role for this SNP in disease pathogenesis. Further work is continuing with larger numbers of patients and in characterizing the functional significance of this polymorphism.
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