Investigation of the association between interleukin-1beta polymorphism and normal tension glaucoma.

PURPOSE: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. The potential similarities in cellular apoptosis leading to neurodegeneration between Alzheimer's disease and NTG were shown in recent studies. The interleukin-1beta (IL-1beta; -511) and IL-1beta (+3953) polymorphisms were found to increase risk with Alzheimer's disease. The purpose of this study was to test the hypothesis that the IL-1beta polymorphism is associated with NTG in the Chinese population. METHODS: This is a cohort study in a Chinese population that involved 231 people with NTG and 245 healthy controls. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Patients and controls were genotyped for the C/T polymorphism at position -511 and +3953 of the IL-1beta gene. Genotypes for NTG and control groups were compared for statistically significant differences. RESULTS: There was no significant difference in genotype frequency or allele frequency distribution of the IL-1beta gene polymorphisms (position -511 and +3953) between NTG patients and the control group (p >0.3). CONCLUSIONS: Our study showed no evidence for an association between the IL-1beta (-511) and IL-1beta (+3953) polymorphisms and NTG. The IL-1beta gene polymorphisms (position -511 and +3953) may not play a key role in NTG pathogenesis in Chinese population.

Normal tension glaucoma is not associated with the interleukin -1alpha (-889) genetic polymorphism.

BACKGROUND: Factors other than intraocular pressure are likely to play a role in the pathogenesis of glaucomatous optic neuropathy, particularly in individuals with normal tension glaucoma (NTG). Recent laboratory evidence has shown that there are potential similarities between Alzheimer disease and NTG in cellular apoptosis leading to neurodegeneration. IL-1alpha (-889) T allele polymorphism has been found to increase the risk of developing Alzheimer disease. The aim of this study was to test in a Chinese cohort the hypothesis that IL-1alpha (-889) polymorphism is associated with NTG. METHODS: One hundred sixty-two unrelated patients with NTG were recruited and compared with 167 controls in a Chinese population. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique. Patients and controls were genotyped for the C/T polymorphism at position -889 of the IL-1alpha gene promoter region. RESULTS: There was no significant difference in the frequency of IL-1alpha (-889) alleles or genotypes in the NTG population compared with that in the control group. CONCLUSIONS: We conclude that C/T polymorphism at position -889 of the IL-1alpha gene promoter region does not increase the risk of developing NTG. However, further studies on NTG are necessary to investigate the genetic basis and factors involved in the development of the neurodegenerative process.

Polymorphism in the IL-1alpha (-889) locus associated with elevated risk of primary open angle glaucoma.

PURPOSE: Recent laboratory evidence indicates that the inflammatory cytokine, interleukin-1 (IL-1), has either protective or adverse effects on primary open angle glaucoma (POAG). Inheritance of the IL-1alpha (-889) polymorphism (the T allele), previously shown to increase IL-1 production, has been associated with an elevated risk of Alzheimer's disease. The neuronal injuries associated with Alzheimer's disease have a number of similarities with the optic nerve changes often seen with POAG. In this report we have explored the possible association between the IL-1alpha (-889) polymorphism and the development of POAG. METHODS: Chinese patients with POAG (156) were recruited and compared with 167 healthy chinese controls. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for the C/T polymorphism at position -889 of the IL-1alpha gene promoter region. RESULTS: The frequency of the IL-1alpha (-889) T allele (21% versus 13%, respectively; p=0.007) and the carriers of the IL-1alpha (-889) T allele (37% versus 25%; p=0.019, OR 1.76, 95%CI 1.1-2.83) were greater in POAG patients compared with controls. There is a higher risk of POAG associated with homozygosity for the IL-1alpha (-889) T allele (TT genotype) compared with the control population (CC genotype; 5% versus 1%, respectively, p=0.04; OR 5.1, 95% CI 1.19-21.66). CONCLUSIONS: The IL-1alpha (-889) T allele polymorphism, previously shown to increase IL-1 gene expression, may be a risk factor in the development of POAG.