Abstract
Hyperhomocysteinemia induced by the C677T genetic variant in MTHFR (methylenetetrahydrofolate reductase) has been implicated in neuronal cell death of retinal ganglion cells (RGC), which is a characteristic feature of glaucoma. However, association of MTHFR C677T with glaucoma has been controversial because of inconsistent results across association studies. Association between MTHFR C677T and glaucoma has not been reported in Indian population. Therefore, with a focus on neurodegenerative death of RGC in glaucoma, the current study aimed to investigate association of MTHFR C677T with Primary Open Angle Glaucoma (POAG) and Primary Angle Closure Glaucoma (PACG) in a North Indian population. A total of 404 participants (231 patients and 173 controls) were included in this study. Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. A few random samples were also tested by direct sequencing. Genotypic and allelic distributions of the POAG and PACG cohorts were compared to that of controls by chi-square test and odds ratios were reported with 95% confidence intervals. Genotypic and allelic distributions between POAG cases and controls were significantly different (p = 0.03 and p = 0.01 respectively). Unlike POAG, we did not find significant difference in the genotypic and allelic distributions of C677T between PACG cases and controls (p>0.05). We also observed a higher proportion of TT associated POAG in females than that in males. However, this is a preliminary indication of gender specific risk of C677T that needs to be replicated in a larger cohort of males and females. The present investigation on MTHFR C677T and glaucoma reveals that the TT genotype and T allele of this polymorphism are significant risk factors for POAG but not for PACG in North Indian population. Ours is the first report demonstrating association of MTHFR C677T with POAG but not PACG in individuals from North India.
Highlights
Glaucoma is the second most threatening eye disease attributable for blindness worldwide [1]
The present study aimed to examine the genetic association of MTHFR C677T with two major forms of glaucoma, Primary Open Angle Glaucoma (POAG) and Primary Angle Closure Glaucoma (PACG), in a subset of the North Indian population belonging to Eastern Uttar Pradesh and Western Bihar
The frequency of the TT genotype (1.16%) and the minor allele frequency (MAF) of the T allele (10.98%) in our control group are similar to those reported in previous studies on C677T and other disorders conducted in the same population [29,30,31,32]
Summary
Glaucoma is the second most threatening eye disease attributable for blindness worldwide [1]. Understanding the genetics of glaucoma is of prime importance, for early detection, and to arrest the progression of the disease. Glaucoma is a multifactorial disease, with multiple genetic and non-genetic factors contributing to its development. Glaucoma encompasses clinically heterogeneous forms, all of which invariably involve a characteristic and progressive optic neuropathy leading to irreversible loss of visual field [4]. Despite this clinical heterogeneity, all forms of glaucoma result in death of retinal ganglion cells (RGC) in the optic nerve. Various molecular studies support apoptotic death of RGC in glaucoma [5,6,7]
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