CYP39A1 G204E variant ups risk of glaucoma, blindness in patients with exfoliation syndrome

Patients with exfoliating syndrome (XFS) who carry the CYP39A1 G204E mutation are at significantly higher risk of blindness, have higher occurrence of exfoliation glaucoma (XFG), and display more severe glaucoma than those with XFS without any CYP39A1 mutation, reveals a study.

Thirty-five patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation, who were randomly selected from the Japanese XFS cohort, were enrolled in this retrospective case study.

The authors estimated the significance of the calculated odds ratio (OR) for all categorical measures using two-sided Fisher exact test with an alpha level <0.05. They also compared the two groups using linear mixed effect models with group as random effect and taking into account possible dependence between eyes within an individual.

Overall, XFS patients carrying the CYP39A1 G204E variant had significantly higher risk for blindness compared with those without any CYP39A1 mutations (28.6 percent vs 5.4 percent; odds ratio [OR], 7.1, 95 percent confidence interval [CI], 2.7‒20.2; p<0.001).

More XFS patients with the CYP39A1 G204E mutation exhibited signs of XFG in at least one eye relative to those in the comparison group (65.7 percent vs 27.3 percent; OR, 5.1, 95 percent CI, 2.4‒11.4; p<0.0001). Carriers also had significantly higher peak intraocular pressure, larger vertical cup-disc ratio, and worse visual field mean deviation (p<0.001).

In addition, patients with the CYP39A1 G204E mutation required more laser or glaucoma surgical interventions than did those without any mutation (51.4 percent vs 21.3 percent; p<0.001).

“Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a twofold increased risk of XFS,” the authors said.