Abstract
BackgroundPrimary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage. An unstable or altered p21 protein could modify the cellular response to genomic injury and abolish the effect of p21. A previous study on a Chinese cohort suggested that the p21 codon 31 polymorphism may alter the state of apoptosis in glaucomatous optic neuropathy, failing to protect the ganglion cells. The aim of this study was to test the hypothesis that a p21 codon 31 polymorphism is associated with POAG on a Caucasian cohort.Methods140 POAG patients and a control group of 73 healthy individuals were included in the study. All the subjects were of Caucasian origin. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for a single nucleotide polymorphism (C/A transversion) in the third base of codon 31 of p21, which leads to a serine (Ser)/arginine (Arg) substitution.ResultsThe distribution of the genotypes in the POAG patients showed 128 (91.4%) Ser homozygotes, 10 (7.1%) Ser/Arg heterozygotes and 2 (1.5%) Arg homozygotes. In the control cohort, there were 61 (83.6%) Ser homozygotes and 12 (16.4%) Ser/Arg heterozygotes. No Arg homozygotes were present amongst the control group. Both the allelic and genotypic frequencies of the Ser or Arg residues at codon 31 were not significantly different between POAG patients and controls (Fisher's exact test, P = 0.20 for alleles and P = 0.0561 for genotypes).ConclusionThis study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG in the Caucasian population.
Highlights
Primary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage
The apoptotic pathway consists of multiple interacting pathways, some of which are still unclear. It appears that, following DNA damage, cells can either proceed to apoptosis or enter a transient arrest cycle, allowing time for DNA repair. p21 gene, known as WAF1 or CIP1, is a key component of this pathway. It can be up-regulated either by activated wild type p53, which acts as a transcription factor [6], or independently, by various factors such as TGFβ, vitamin D, TPA and nerve growth factor. p21 expression results in inhibition of the cyclin-dependent kinases (Cdks), that are essential for cell division
The control group consisted of the spouses of our POAG patients, who were free from any coexisting ocular pathology and had normal visual acuity, intraocular pressure (IOP), visual fields and optic discs
Summary
Primary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage. Primary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. BMC Ophthalmology 2005, 5:5 http://www.biomedcentral.com/1471-2415/5/5 the pathophysiology [3,4] Irrespectively of the causative factors leading to visual loss, most of which are still not understood, the final common pathway in POAG is retinal ganglion cell death, mediated by apoptosis, a genetically regulated process [5]. The apoptotic pathway consists of multiple interacting pathways, some of which are still unclear It appears that, following DNA damage, cells can either proceed to apoptosis or enter a transient arrest cycle, allowing time for DNA repair. Cell cycle is arrested at the G1 phase, until genomic repair is established
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