Genetic analysis points to apoptotic mutation in glaucoma

A major cause of blindness may, after all, stem from changes in gene p53, contrary to other data, according to a study showing a link with p53 haplotypes in a Caucasian population. This is further evidence to support programmed cell death in causing primary open angle glaucoma (POAG).

The distribution of haplotypes with two polymorphic variants—a 16 base pair insertion in intron 3 and C to G base pair (proline to arginine) change at codon 72 in exon 4—within the p53 gene was significantly different between patients with POAG and controls. Of the four possible haplotypes, only subjects with the insertion-arginine haplotype were significantly more likely to have glaucoma—12.5% versus 0.68% for controls.

The study compared frequency distribution of p53 haplotypes between 140 unrelated patients with POAG and 73 unrelated healthy age and sex matched controls with clear differences in cardinal measures of POAG between them. Haplotypes were identified by p53 gene amplification and RFLP analysis.

Other studies have not shown an association between p53 variants and disease. The authors of this study interpret this as a result of methodological differences and to the notion that neither variant is the key variant, but that this is in linkage disequilibrium with the insertion-arginine haplotype.

POAG affects 70 million people world wide. Research has indicated that multiple genes may play a part, and the discovery that apoptosis of retinal ganglion cells is an important cause of glaucoma has raised the possibility that both may determine susceptibility.