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WDR36 variants in East Indian primary open-angle glaucoma patients.

作者信息

Mookherjee Suddhasil, Chakraborty Subhadip, Vishal Mansi, Banerjee Deblina, Sen Abhijit, Ray Kunal

机构信息

Molecular & Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

出版信息

Mol Vis. 2011;17:2618-27. Epub 2011 Oct 8.


DOI:
PMID:22025897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3198481/
Abstract

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies with a complex genetic basis. To date, only the following four genes have been identified: viz. myocilin (MYOC), optineurin (OPTN), WD repeat domain 36 (WDR36), and neurotrophin 4 (NTF4). However, there are conflicting reports regarding the involvement of WDR36 in the pathogenesis of primary open-angle glaucoma (POAG). In the Asian population, mutations in WDR36 appear to play a minor role in POAG pathogenesis but polymorphic variants have been found to be associated with POAG, especially in patients with high tension glaucoma (HTG). The purpose of this study is to determine the role of WDR36 in East Indian POAG patients. To date, no other studies have yet examined this role. METHODS: Ten single nucleotide polymorphisms (SNPs; rs1971050, rs1993465, rs13153937, rs10038177, rs11241095, rs10043631, rs10038058, rs10491424, rs17553936, and rs13186912) spanning almost the entire WDR36 gene were selected and their association with eastern Indian POAG patients was evaluated. Our study pool consisted of 323 POAG patients. Of these 116 were patients who had HTG with intraocular perssure (IOP) >21mmHg and 207 were found to be non-HTG patients (presenting IOP<21mmHg). The study also included 303 participants as controls. The polymorphisms were genotyped in both the patients and the controls using the PCR-RFLP method. Moreover, the SNP that showed significant association was validated by DNA sequencing. The haplotypes were obtained using Haploview 4.1 software. The allele and haplotype frequencies were compared between the patient group and the control group using Pearson's χ(2) test. RESULTS: First, we genotyped the selected SNPs in the 323 POAG patients and 119 of the participants in the control group, in which only rs10038177 (c.710+30C>T) was found to be strongly associated with the HTG cases (OR=2.186; 95% CI=1.458-3.277; p=1.4×10(-4)). To increase the significance of the study, the SNP was genotyped in an additional 184 of the participants in the control group and it was observed that the SNP retained the association (OR=1.216; 95% CI=1.064-2.306; p=0.002). However, no haplotype was found to have any sustainable association with POAG. Based on the LD pattern and location of rs10038177, exon 5 of WDR36 was sequenced but no suspected disease-causing variant was detected. CONCLUSIONS: Our study suggests a possible association between WDR36 SNP in a cohort of eastern Indian POAG patients who also have high intraocular pressure (IOP). This study needs to be further validated in a larger patient cohort.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7581/3198481/a51867a1026c/mv-v17-2618-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7581/3198481/a71b3288336d/mv-v17-2618-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7581/3198481/a51867a1026c/mv-v17-2618-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7581/3198481/a71b3288336d/mv-v17-2618-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7581/3198481/a51867a1026c/mv-v17-2618-f2.jpg

相似文献

[1]
WDR36 variants in East Indian primary open-angle glaucoma patients.

Mol Vis. 2011

[2]
Different WDR36 mutation pattern in Chinese patients with primary open-angle glaucoma.

Mol Vis. 2009

[3]
Multiple gene polymorphisms analysis revealed a different profile of genetic polymorphisms of primary open-angle glaucoma in northern Chinese.

Mol Vis. 2009

[4]
Association of IL1A and IL1B loci with primary open angle glaucoma.

BMC Med Genet. 2010-6-19

[5]
Association of WDR36 polymorphisms with primary open angle glaucoma: A systematic review and meta-analysis.

Medicine (Baltimore). 2017-6

[6]
Role of CYP1B1, MYOC, OPTN, and OPTC genes in adult-onset primary open-angle glaucoma: predominance of CYP1B1 mutations in Indian patients.

Mol Vis. 2007-4-30

[7]
Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese.

Mol Vis. 2007-10-9

[8]
SNPs and interaction analyses of myocilin, optineurin, and apolipoprotein E in primary open angle glaucoma patients.

Mol Vis. 2005-8-29

[9]
Mutations in MYOC gene of Indian primary open angle glaucoma patients.

Mol Vis. 2002-11-15

[10]
An Application of NGS for Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma.

Int J Med Sci. 2017-9-20

引用本文的文献

[1]
Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma.

PLoS One. 2024

[2]
Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives.

Int J Mol Sci. 2023-8-23

[3]
-Associated Neurodegeneration: A Case Report Highlights Possible Mechanisms of Normal Tension Glaucoma.

Genes (Basel). 2021-10-15

[4]
Research progress on human genes involved in the pathogenesis of glaucoma (Review).

Mol Med Rep. 2018-5-23

[5]
An Application of NGS for Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma.

Int J Med Sci. 2017-9-20

[6]
Association of WDR36 polymorphisms with primary open angle glaucoma: A systematic review and meta-analysis.

Medicine (Baltimore). 2017-6

[7]
Major review: Molecular genetics of primary open-angle glaucoma.

Exp Eye Res. 2017-7

[8]
Genetics of primary open angle glaucoma.

Jpn J Ophthalmol. 2013-11-21

[9]
Mitochondrial genome analysis of primary open angle glaucoma patients.

PLoS One. 2013-8-5

本文引用的文献

[1]
Complex genetic mechanisms in glaucoma: an overview.

Indian J Ophthalmol. 2011-1

[2]
Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro.

Hum Mol Genet. 2010-11-3

[3]
Association between primary open-angle glaucoma (POAG) and WDR36 sequence variance in Italian families affected by POAG.

Br J Ophthalmol. 2010-9-2

[4]
Identification of a novel mutation in the NTF4 gene that causes primary open-angle glaucoma in a Chinese population.

Mol Vis. 2010-8-15

[5]
Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice.

Hum Mol Genet. 2010-7-14

[6]
Molecular complexity of primary open angle glaucoma: current concepts.

J Genet. 2009-12

[7]
Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma.

Am J Hum Genet. 2009-10

[8]
Different WDR36 mutation pattern in Chinese patients with primary open-angle glaucoma.

Mol Vis. 2009

[9]
Glaucoma-associated WDR36 variants encode functional defects in a yeast model system.

Hum Mol Genet. 2009-4-1

[10]
Multiple gene polymorphisms analysis revealed a different profile of genetic polymorphisms of primary open-angle glaucoma in northern Chinese.

Mol Vis. 2009

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