The Methylentetrahydrofolate Reductase Gene Polymorphism Is Associated With Open Angle Glaucoma in the Japanese Population

Abstract

Purpose: : To assess whether single nucleotide polymorphisms in the methylentetrahydrofolate reductase (MTHFR) gene is associated with open angle glaucoma (OAG) in the Japanese population.

Methods: : Genomic DNA was examined in a cohort of 192 Japanese patients with normal tension glaucoma (NTG), 186 patients with primary open angle glaucoma (POAG), and 181 control subjects. The average age was 63.7 ± 13.3 years (mean ± SD) for the NTG patients, 62.5 ± 15.0 years for the POAG patients, and 65.4 ± 11.4 years for the control subjects. The presence or absence of OAG in patients and controls was based on clinical examination and/or ophthalmic records. The A1298C polymorphism in the MTHFR gene was genotyped using Pyrosequencing^TM analysis, and compared between OAG patients and control subjects. The associations between clinical data, such as age at diagnosis, refractive error, maximum intraocular pressure (IOP), and the A1298C polymorphism were also evaluated.

Results: : There was a significant difference in the A1298C genotype frequencies between the OAG and control groups (P = 0.0015 Chi–square test), and the frequency of the C allele was significantly higher in the NTG and POAG patients compared to the control subjects (17.2% vs. 9.9%, P = 0.0040 and 17.7% vs. 9.9%, P = 0.0027 respectively, Fisher exact test). Adjusted for age, gender, refractive error, and maximum IOP, appropriate threefold increased risk of NTG (P = 0.0008, odds ratio [OR] 2.91, 95% confidence interval [CI] 1.56 to 5.41) was found with the C allele in the A1298C polymorphism. The age at diagnosis (51.3 ± 15.3 years) in the POAG patients with the CC or AC genotypes in the A1298C polymorphism tended to be lower (P = 0.074, student t–test) than that (55.7 ± 15.6 years) with the AA genotype.

Conclusions: : The MTHFR gene polymorphism is associated with OAG in the Japanese population. Further studies in the other ethnic populations should be performed to elucidate the relationship between the MTHFR gene and OAG.

Keywords: candidate gene analysis • genetics