Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese

Area of Science:

• Ophthalmology
• Human Genetics

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide.
• Genetic factors play a significant role in the pathogenesis of POAG, but specific causative genes are still being identified.

Purpose of the Study:

• To investigate the association between mutations in the WD repeat domain 36 gene (WDR36) and primary open-angle glaucoma (POAG) in the Japanese population.
• To analyze WDR36 mutations separately in patients with high tension glaucoma (HTG) and normal tension glaucoma (NTG).

Main Methods:

• Genomic DNA was extracted from 136 unrelated Japanese patients with HTG and 103 unrelated patients with NTG.
• All 23 exons of the WDR36 gene were amplified using polymerase chain reaction (PCR) and subjected to bidirectional sequencing.

Main Results:

• Twenty sequence alterations in WDR36 were identified, including 10 novel variants.
• The p.I264V and c.1965-30A>G variants showed a significantly higher frequency in the HTG group compared to controls.
• A nonsynonymous variant, p.S664L, was found in one HTG patient.

Conclusions:

• The identified WDR36 variants, particularly p.I264V and c.1965-30A>G, are associated with high tension glaucoma in Japanese patients.
• These findings suggest that WDR36 gene mutations likely contribute to the pathogenesis of HTG.