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Nicole A. Carnt, Mark D. Willcox, Scott Hau, Linda Garthwaite, Victoria Evans, Cherry F. Radford, John Dart, Subhabrata Chakrabarti, Fiona Stapleton; Association Of Single Nucleotide Polymorphisms Of Interleukins 1β, 6 And 12b With Contact Lens Keratitis Susceptibility And Severity. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4692.
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To investigate whether single nucleotide polymorphisms in IL-1 ß, IL-6 and IL-12 ß are associated with the susceptibility and severity of contact lens related keratitis.
One hundred and twelve cases keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and in Australia during 2003-2005. Buccal swab samples were collected on Whatman FTA cards and were mailed by post for analysis. IL-1ß (-31), IL-6 (-174, -572, -597) and IL-12 B (3'+1158) genotypes were determined with pyrosequencing. Analysis using a regressionmodel for susceptibility (sterile, microbial keratitis, controls) and severity was conducted for allele, genotype and haplotype frequencies. Statistical significance was set at 0.05.
Carriers of IL-6 single nucleotide polymorphisms were more likely to experience moderate and severe events compared to those with non-mutated genotypes (-174 heterozygous, odds ratio, OR 3.1, 95% confidence interval, CI 1.1 - 8.3; homozygous, OR 6.4, 95% CI 1.4 - 28.4; -174/-597, OR 4.1, 95% CI 1.6-11.0). More severe keratitis and microbial keratitis were less likely to occur inwearers with the non-mutated IL-6 haplotype (severity OR 0.4, 95% CI 0.2-0.7, microbial OR 0.6, 95% CI 0.4-0.9). Wearers carrying an IL-12B SNP had an increased risk of sterile keratitis (OR 9.7, 95% CI, 1.2 - 76.9) compared to controls.
IL-6 single nucleotide polymorphisms are known to reduce protein expression of this cytokine and thus ocular immune defence, and carriers of these SNPs were more likely to experience more severe and microbial keratitis suggesting that IL-6 decreases the severity and susceptibility of contact lens related keratitis. Carriers of a functional SNP of IL-12B that is known to increase IL-12 expression and stability are more likely to experience sterile keratitis, suggesting that this is associated with the intense inflammatory reaction that occurs in this condition.
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