Distribution of p53 codon 72 polymorphism in Indian primary open angle glaucoma patients.
Distribution of p53 codon 72 polymorphism in Indian primary open angle glaucoma patients.
复制标题
印度原发性开角型青光眼患者中 p53 密码子 72 多态性的分布。
作者：
Moulinath Acharya;S. Mitra;A. Mukhopadhyay;Mita Khan;S. Roychoudhury;K. Ray
目的
青光眼是一种复杂的眼部神经退行性疾病。原发性开角型青光眼（POAG）是最常见的类型，占总病例的一半以上。最近，中国血统对照受试者和 POAG 患者之间抑癌基因 p53 密码子 72 多态性的分布存在显着差异 (p=0.00782)。相对于健康对照，POAG 患者的 p53 基因密码子 72 处的脯氨酸残基明显过多。本研究的目的是调查所报道的 p53 多态性与 POAG 之间的关联是否是一种常见现象，与人口的地理位置或种族无关。
方法
67 名不相关的 POAG 患者，年龄范围为 10-65 岁（平均值+/-SD 为 41.16+/-18.52 岁），以及 112 名年龄范围相似的 18-63 岁对照受试者（平均值+/-SD 为 36.64+/-14.65 岁）纳入本研究。 p53 基因的一个区域包含两个多态性位点，即内含子 3 中的 16 bp 重复和外显子 4 中的 BstU I RFLP，通过聚合酶链反应从印度 POAG 患者和正常健康对照中扩增。密码子 72 中的单个碱基变化（G 至 C）将氨基酸残基从精氨酸更改为脯氨酸，并去除了上述多态性 BstU I 位点。扩增的 DNA 片段用限制性酶消化，片段的消化模式用于鉴定两个多态性位点的等位基因。
结果
通过分析密码子 72 多态性 (p=0.5627) 或内含子 16 bp 重复多态性 (p=0.059)，未观察到 p53 等位基因与印度 POAG 患者之间存在显着关联。据报道，单倍型分析可以更好地预测 p53 基因与不同类型癌症的关联，也进行了该分析，但没有检测到任何单倍型与 POAG 的关联 (p=0.1831)。
结论
密码子 72 处编码脯氨酸的 p53 基因与 POAG 之间的关联可能存在于某些种族人群中，但不能用作该基因作为导致 POAG 的视网膜神经节细胞死亡的常见调节因子的作用的预测因子。
PURPOSE
Glaucoma is a complex neurodegenerative disorder of the eye. Primary Open Angle Glaucoma (POAG) is the most common type, accounting for over half of the total cases. Recently, a significant difference in the distribution of the codon 72 polymorphism of the tumor suppressor gene p53 between control subjects and POAG patients of Chinese origin (p=0.00782) was demonstrated. The proline residue at codon 72 of the p53 gene was significantly over represented in the POAG patients relative to healthy controls. The purpose of this study was to investigate whether the reported association between the p53 polymorphism and POAG is a common phenomenon irrespective of geographical location or ethnicity of the population.
METHODS
Sixty seven unrelated POAG patients, ranging from 10-65 years of age (mean+/-SD of 41.16+/-18.52 years), and 112 control subjects having a similar age range of 18-63 years (mean+/-SD of 36.64+/-14.65 years) were enrolled in this study. A region of the p53 gene encompassing two polymorphic sites, a 16 bp duplication in intron 3 and a BstU I RFLP in exon 4, were amplified by polymerase chain reaction from Indian POAG patients and normal healthy controls. A single base change (G to C) in codon 72 alters the amino acid residue from arginine to proline and removes the polymorphic BstU I site mentioned above. The amplified DNA fragments were digested with the restriction enzyme and the digestion patterns of the fragments were used to identify the alleles for both the polymorphic sites.
RESULTS
No significant association between p53 alleles and Indian POAG patients were observed by analyzing either codon 72 polymorphism (p=0.5627) or the intronic 16 bp duplication polymorphism (p=0.059). Haplotype analysis, reported to be a better predictor of association of the p53 gene with different types of cancer, was also performed and no association of any haplotype was detected with POAG (p=0.1831).
CONCLUSIONS
Association between the p53 gene encoding for proline at codon 72 and POAG presumably exists in some ethnic populations but cannot be used as a predictor for the role of the gene as a common regulator of cell death of retinal ganglions leading to POAG.