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巴基斯坦旁遮普省中东部人群中,PLEKHA7基因单核苷酸多态性与原发性闭角型青光眼(PACG)的遗传关联。

Genetic association of single nucleotide polymorphisms in PLEKHA7 gene with primary angle closure glaucoma (PACG) in a Central-Eastern Punjab cohort of Pakistan.

作者信息

Asif Roha, Khalid Ammara, Bashir Rasheeda, Aslam Komal, Yousaf Khazeema, Waseem Raazia

机构信息

Department of Biotechnology, Lahore College for Women University, Lahore, 54000, Pakistan.

Department of Biotechnology, Kinnaird College for Women, Lahore, Pakistan.

出版信息

Mol Biol Rep. 2025 Feb 4;52(1):191. doi: 10.1007/s11033-025-10292-x.


DOI:10.1007/s11033-025-10292-x
PMID:39903387
Abstract

BACKGROUND: Primary Angle Closure Glaucoma (PACG) is a potentially devastating disease that causes optic nerve injury globally. METHODS: The enrollment of patients with PACG and healthy controls came from ophthalmology health centers in different hospitals in Punjab (n = 96 cases and n = 102 controls). PLEKHA7 rs216489 and rs11024102 alleles were genotyped by Tetra ARMS PCR. Binary Logistic Regression was applied to discover the relationship amid risk alleles with PLEKHA7. Genetic models were used to identify the risk of links among a specific inheritance pattern's genotype and phenotype. In silico analysis was performed to analyze the functional consequences and regulatory elements of both these polymorphisms. RESULTS: This study investigated that the patients affected with PACG have IOP and C/D ratio (17.43 ± 9.40 and 0.565 ± 0.5994 respectively) along with other clinical characteristics than healthy controls. The genotype distribution for PLEKHA7 rs216489 revealed no association with PACG. In contrast, in SNP rs11024102, the frequency of genotype AA is noticeably higher in PACG patients compared to controls. For genetic models, the dominant model of rs11024102 (P < 0.02) (OR = 2.335, 95% CI = 1.135-4.804) was discovered to be strongly associated to rise the pathogenicity of PACG. In silico examination predicted that both of the SNPs of the PLEKHA7 gene are causing benign mutations in nature and are less and more likely to be predicted as regulatory variants. CONCLUSION: This is the first study on PACG genotypes from Pakistan, and results suggest that PLEKHA7 (rs11024102) polymorphism is significantly associated with susceptibility to PACG in Punjab, Pakistan.

摘要

背景:原发性闭角型青光眼(PACG)是一种在全球范围内可导致视神经损伤的潜在毁灭性疾病。 方法:PACG患者和健康对照的招募来自旁遮普邦不同医院的眼科健康中心(96例患者和102例对照)。通过四引物扩增受阻突变系统PCR对PLEKHA7 rs216489和rs11024102等位基因进行基因分型。应用二元逻辑回归来发现PLEKHA7风险等位基因之间的关系。遗传模型用于确定特定遗传模式的基因型和表型之间联系的风险。进行了计算机模拟分析以分析这两种多态性的功能后果和调控元件。 结果:本研究调查发现,与健康对照相比,PACG患者除其他临床特征外,眼压和杯盘比分别为(17.43±9.40和0.565±0.5994)。PLEKHA7 rs216489的基因型分布与PACG无关联。相比之下,在SNP rs11024102中,PACG患者中基因型AA的频率明显高于对照。对于遗传模型,发现rs11024102的显性模型(P<0.02)(OR = 2.335,95%CI = 1.135 - 4.804)与PACG致病性增加密切相关。计算机模拟检查预测,PLEKHA7基因的两个SNP在本质上都导致良性突变,并且被预测为调控变异体的可能性越来越小。 结论:这是来自巴基斯坦的关于PACG基因型的第一项研究,结果表明PLEKHA7(rs11024102)多态性与巴基斯坦旁遮普邦PACG易感性显著相关。

相似文献

[1]
Genetic association of single nucleotide polymorphisms in PLEKHA7 gene with primary angle closure glaucoma (PACG) in a Central-Eastern Punjab cohort of Pakistan.

Mol Biol Rep. 2025-2-4

[2]
Extended association study of PLEKHA7 and COL11A1 with primary angle closure glaucoma in a Han Chinese population.

Invest Ophthalmol Vis Sci. 2014-5-22

[3]
Genetic associations in PLEKHA7 and COL11A1 with primary angle closure glaucoma: a meta-analysis.

Clin Exp Ophthalmol. 2015-8

[4]
Genotype-phenotype correlation analysis for three primary angle closure glaucoma-associated genetic polymorphisms.

Invest Ophthalmol Vis Sci. 2014-2-24

[5]
In-depth analysis of eight susceptibility loci of primary angle closure glaucoma in Han Chinese.

Exp Eye Res. 2021-1

[6]
[Association of PLEKHA7, COL11A1 and PCMTD1-ST18 gene polymorphisms with primary angle closure glaucoma in ethnic Han Chinese from Sichuan].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2016-8

[7]
Association study in a South Indian population supports rs1015213 as a risk factor for primary angle closure.

Invest Ophthalmol Vis Sci. 2013-8-19

[8]
Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci for Estimating Angle Closure Disease Severity.

Ophthalmology. 2021-3

[9]
Association of genetic variants with primary angle closure glaucoma in two different populations.

PLoS One. 2013-6-28

[10]
Impact of rs11024102 PLEKHA7, rs3753841 COL11A1 single nucleotide polymorphisms, and serum levels of oxidative stress markers on the risk of primary angle-closure glaucoma in Egyptians.

J Genet Eng Biotechnol. 2022-8-29

本文引用的文献

[1]
Paracingulin recruits CAMSAP3 to tight junctions and regulates microtubule and polarized epithelial cell organization.

J Cell Sci. 2024-3-1

[2]
Origin and Evolution of the Multifaceted Adherens Junction Component Plekha7.

Front Cell Dev Biol. 2022-3-23

[3]
Genetic Markers PLEKHA7, ABCC5, and KALRN Are Not Associated With the Progression of Primary Angle Closure Glaucoma (PACG) in Malays.

Cureus. 2021-10-16

[4]
Detection of Primary Angle Closure Glaucoma Progression by Optical Coherence Tomography.

J Glaucoma. 2021-5-1

[5]
Coding Variants in and May Contribute to Risk of Primary Angle Closure Glaucoma.

DNA Cell Biol. 2020-5-12

[6]
A comprehensive study capturing vision loss burden in Pakistan (1990-2025): Findings from the Global Burden of Disease (GBD) 2017 study.

PLoS One. 2019-5-3

[7]
COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity.

J Ophthalmol. 2019-1-27

[8]
Mutations in the Epithelial Cadherin-p120-Catenin Complex Cause Mendelian Non-Syndromic Cleft Lip with or without Cleft Palate.

Am J Hum Genet. 2018-5-24

[9]
Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci in Patients with Early Stages of Angle-Closure Disease.

Ophthalmology. 2018-1-6

[10]
Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

Hum Mol Genet. 2017-10-15

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