Polymorphism in the TNF-α(−863) locus associated with reduced risk of primary open angle glaucoma

Purpose: Tumor necrosis factor-α (TNF-α), an important proinflammatory cytokine, exerts a variety of physiologic and pathogenic effects that lead to tissue destruction. Recent laboratory evidence indicates that TNF-α have either protective or adverse effects on primary open angle glaucoma (POAG). Inheritance of the TNF-α (−863) C allele has been associated with an elevated risk of Alzheimer disease. The neuronal injuries associated with Alzheimer disease have several similarities with the optic nerve changes often seen with POAG. In this study we investigated the possible association between the TNF-α (−863) polymorphism and the development of POAG. Methods: A total of 234 patients with POAG were recruited and compared with 230 healthy controls in a Chinese population. Sequence-specific primers with 3′ end mismatches were used to identify the presence of specific allelic variants by polymerase chain reaction (PCR) amplification. Patients and controls were genotyped for the A/C polymorphism at position −863 of the TNF-α gene promoter region. Results: The frequency of the TNF-α (−863)A allele (22% versus 30%, respectively; p=0.007) and the carriers of the TNF-α (−863)A allele (37% versus48%; p=0.017, OR 0.63, 95% CI 0.44–0.92) were lower in POAG patients compared with those in controls. There is a reduced risk of POAG associated with homozygosity for the TNF-α (−863)A allele (AA genotype) compared with that in the control population (AA genotype; 7% versus 11%, respectively, p=0.037; OR 0.5, 95% CI 0.26–0.98). Conclusions: The TNF-α (−863)A allele polymorphism may be a protective factor in the development of POAG. Glaucoma is a progressive optic neuropathy characterized by degeneration of retinal ganglion cells, cupping of the optic nerve heads and visual field defects often related to elevated intraocular pressure. Glaucoma affects 70 million people worldwide, and constitutes the second largest cause of bilateral blindness in the world [1]. Primary open angle glaucoma (POAG) is a multifactorial neurodegenerative disease. Both genetic and environmental factors are thought to contribute to the pathophysiology of the disease. Glaucoma is a complex clinical trait and its inheritance has been shown to follow both Mendelian and non-Mendelian models [2]. At least eight loci of genes have been found to be associated with POAG, such as myocilin (MYOC), optineurin (OPTN) and WD repeat domain 36 (WDR36) [3-6]. Mutation in the optineurin gene was initially reported in 16.7% of families with hereditary POAG, with most of them having normal tension glaucoma [4]. Cytochrome P450, family 1, subfamily B, polypeptide 1(CYP1B1) and latent-transforming