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

Mookherjee S, Chakraborty S, Vishal M, Banerjee D, Sen A, Ray K - Mol. Vis. (2011)

Bottom Line: 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).Moreover, the SNP that showed significant association was validated by DNA sequencing.This study needs to be further validated in a larger patient cohort.

View Article: PubMed Central - PubMed

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

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.

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Related in: MedlinePlus

Schematic representation of WDR36 with the location of SNPs selected for the study. The sizes of exons and introns shown in the illustration are not according to scale.
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f1: Schematic representation of WDR36 with the location of SNPs selected for the study. The sizes of exons and introns shown in the illustration are not according to scale.

Mentions: We selected 10 SNPs (rs1971050, rs1993465, rs13153937, rs10038177, rs11241095, rs10043631, rs10038058, rs10491424, rs17553936, and rs13186912) based on previous reports of the association between POAG and the SNP location, such that the SNPs spans the entire WDR36 gene (Figure 1). In the first phase of the study, all the SNPs were genotyped in all 323 of the POAG patients and in 119 of the controls.


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

Mookherjee S, Chakraborty S, Vishal M, Banerjee D, Sen A, Ray K - Mol. Vis. (2011)

Schematic representation of WDR36 with the location of SNPs selected for the study. The sizes of exons and introns shown in the illustration are not according to scale.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198481&req=5

f1: Schematic representation of WDR36 with the location of SNPs selected for the study. The sizes of exons and introns shown in the illustration are not according to scale.
Mentions: We selected 10 SNPs (rs1971050, rs1993465, rs13153937, rs10038177, rs11241095, rs10043631, rs10038058, rs10491424, rs17553936, and rs13186912) based on previous reports of the association between POAG and the SNP location, such that the SNPs spans the entire WDR36 gene (Figure 1). In the first phase of the study, all the SNPs were genotyped in all 323 of the POAG patients and in 119 of the controls.

Bottom Line: 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).Moreover, the SNP that showed significant association was validated by DNA sequencing.This study needs to be further validated in a larger patient cohort.

View Article: PubMed Central - PubMed

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

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.

Show MeSH
Related in: MedlinePlus