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M. Fini, C.–Y. Wang, P.J. Farthing–Nayak, D.L. Budenz, L.M. Ventura, M. Polk, A. Venkatramen, M.B. Gorin, J.S. Schuman, Miami–Pittsburgh Glaucoma Genetics Group; Polymorphisms in the IL–1 Gene Cluster Associated With Reduced Risk for Primary Open Angle Glaucoma in Caucasians . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2369.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We discovered a stress response specific to the eye’s aqueous outflow pathway that provides the first known diagnostic indicator of glaucoma (Wang et al., Nat. Med. 2001). The response is specifically activated in the trabecular meshwork (TM) cells, controlled by an Interleukin–1 (IL–1) autocrine feedback loop through transcription factor NF–ΚB. We showed that activation of the stress response protects TM cells against oxidative stress and may also be compensatory, acting to lower intraocular pressure. The IL–1α promoter allele T variant (–889T) exhibits higher levels of IL–1α expression relative to the more prevalent (–889C) C allele. The two IL–1ß T allele variants, (–511T) and (+3953T) result in higher IL–1ß accumulation in comparison to the more prevalent alleles. We hypothesized that people with the IL–1α and Il–1ß variants, IL–1α (–889T), IL–1ß (–511T) and IL–1ß (+3953T) would have reduced risk of primary open angle glaucoma (POAG). Methods: We assessed genomic DNA from 100 subjects with POAG and 104 normal people drawn from the United States caucasian populations of Miami, Pittsburgh, and Boston by polymerase chain reaction–based analysis. Logistic–regression methods were used to determine the potential effect of each genotype, allele, haplotype and the interaction between them on the risk of glaucoma. Results: The IL–1ß T variant (+3953C–>T) was more highly associated with normal subjects than subjects with POAG. (Odds ratio 0.52, 95%CI 0.27–0.98, p=0.04). The allele frequency of IL–1α (–889T) was borderline higher in the normal control (39%) than in glaucoma group. (20%, p=0.056). The genotype or allele frequencies of IL–1ß (–511C/T) showed there are no difference between the POAG and the control . The "TT" haplotype of IL1ß–3953 and IL1ß–511 and the "TTT" haplotype of IL1α–889, IL1ß–3953 and IL1ß–511 are more common in the control group with score statistics of –2.78 and –3.01 and empirical P–values of 0.006 and 0.002 respectively. Conclusions: The IL–1ß (+3953T) polymorphism may protect an individual against developing POAG.
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