TNF-857T, a genetic risk marker for acute anterior uveitis.
OBJECTIVE
To determine the association between 17 single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha, lymphotoxin-alpha, and the TNF-receptors genes (TNF, LTA, and TNFRSF1A and -B) and idiopathic acute anterior uveitis (IAU) and to investigate their association with HLA-B27 and/or the development of visually significant complications.


METHODS
Ninety-eight white patients in the United Kingdom were identified (by SL) from the uveitis clinics of Moorfields Eye Hospital (London, UK). Sequence-specific primers with 3' end mismatches were used to identify the presence of specific allelic variants by PCR amplification.


RESULTS
There was a significant increase in the frequency of the TNF-857T allele in patients with IAU when compared with control subjects (15.3% vs. 7.3%, P = 0.0006). The frequency of haplotype 4, containing the T allele at nucleotide position -857, was also significantly increased in patients with IAU compared with control subjects (15.4% vs. 7.1%, P = 0.0003, OR 2.4, 95% confidence interval 1.4-4.0). In subgroup analysis, there were significant differences in the frequencies of the uncommon TNFRSF1A-201T and TNFRSF1A-1135T alleles between HLA-B27(+) patients with inflammation-related complications and those without complications (80.0% vs. 33.6%, P = 0.006; 80.0% vs. 36.6%, P = 0.01, respectively).


CONCLUSIONS
A significant difference in the frequency of TNF-857T allele was found in patients with IAU. There was a trend toward the development of inflammation-related complications in HLA-B27(+) patients with IAU who were carriers of TNFRSF1A-201T or TNFRSF1A-1135T alleles. Genetic variations in these proinflammatory mediators and their receptors appear to influence the susceptibility and severity of the inflammatory response within the eyes of patients during the development of IAU.
Kuo
Ni-Wen
NW
Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, United Kingdom.
Lympany
Penny A
PA
Menezo
Victor
V
Lagan
Anna L
AL
John
Sally
S
Yeo
Tun Kuan
TK
Liyanage
Sidath
S
du Bois
Roland M
RM
Welsh
Kenneth I
KI
Lightman
Susan
S
D000208:Acute Disease; D000483:Alleles; D017931:DNA Primers; D005260:Female; D005819:Genetic Markers; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012307:Risk Factors; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014606:Uveitis, Anterior / Q000235:genetics*
D017931:DNA Primers; D005819:Genetic Markers; D015796:HLA-B27 Antigen; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1