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% versus 48%; 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.