title: MTHFR C677T predisposes to POAG but not to PACG in a North Indian population: a case control study.
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.
authors: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
authors: Shashank
authors: S
authors: Gupta
authors: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
authors: Pradeep Kumar
authors: PK
authors: Bhaskar
authors: Department of Zoology, Banaras Hindu University, Varanasi, India.
authors: Ritu
authors: R
authors: Bhardwaj
authors: Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors: Abhishek
authors: A
authors: Chandra
authors: R. K. Netralaya Eye Hospital & Research Centre, Varanasi, India.
authors: Vidya Nair
authors: VN
authors: Chaudhry
authors: R. K. Netralaya Eye Hospital & Research Centre, Varanasi, India.
authors: Prashaant
authors: P
authors: Chaudhry
authors: Centre for Genetic Disorders, Banaras Hindu University, Varanasi, India.
authors: Akhtar
authors: A
authors: Ali
authors: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
authors: Ashim
authors: A
authors: Mukherjee
authors: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
authors: Mousumi
authors: M
authors: Mutsuddi
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015812:Glaucoma, Angle-Closure / Q000453:epidemiology / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)