Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study

Abstract Objective: The genetic spectrum of primary open-angle glaucoma (POAG) in middle-eastern Saudi's is still elusive. To this end, we investigated an association between rs693421, rs2499601 and their haplotypes at chromosome 1q43 locus with POAG and its clinical phenotypes. Genotyping was performed with TaqMan® assays. Haplotypes and their interaction analysis were carried out by SHEsis and SNPStats online tools. Results: The minor “T” allele frequency of rs693421 was 0.48 in controls and 0.52 in cases (odds ratio (OR)=1.15, 95% confidence interval (CI)=0.85–1.54, p=0.368). Similarly, for rs2499601, the minor “C” allele frequency was 0.49 in controls as compared to 0.53 in cases (OR=1.19, 95% CI=0.89–1.60, p=0.236). Besides, genotype distribution for both these polymorphisms was also not significant in additive, dominant and recessive models. rs693421 and rs2499601, showed significant linkage disequilibrium (D’ statistics = 0.69, p<0.001) but haplotype association was non-significant (p=0.698). The significance did not vary after adjustment to age and sex. No significant genotype association was observed with intraocular pressure, cup/disc ratio and number of anti-glaucoma medication in POAG group. Furthermore, age, sex and genotypes did not contribute any significant risk of POAG in regression analysis. We report no association between rs693421, rs2499601 and their haplotypes with POAG and related phenotypes.

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Optic disc haemorrhage and primary open-angle glaucoma: a clinical review

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-314583 ◽

2020 ◽

pp. bjophthalmol-2019-314583 ◽

Cited By ~ 1

Author(s):

Uma Jasty ◽

Alon Harris ◽

Brent Siesky ◽

Lucas W Rowe ◽

Alice C Verticchio Vercellin ◽

...

Keyword(s):

Risk Factors ◽

Optic Disc ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Treatment Strategies ◽

Significant Risk ◽

Female Gender ◽

Open Angle ◽

Increased Risk ◽

Disc Haemorrhage

Studies have confirmed that optic disc haemorrhage (ODH) is a significant risk factor for the development and progression of primary open-angle glaucoma (POAG). Various populations have differing risk factors for developing POAG. As such, a literature review was conducted examining seven studies published in India, China, Japan, Australia, Korea and the USA. The goal of this review was to better identify ODH risk factors and their relationship to development and progression of POAG. Ultimately, patients with ODH have a greater risk for developing POAG across all populations analysed in this review. However, some populations demonstrated additional risk factors for ODH, such as increasing age and female gender. Paradoxically, data from several studies show that people of African descent have a reduced risk of ODH despite having increased risk of open-angle glaucoma than their Caucasian counterparts. By parsing out the complex relations between ODH and open-angle glaucoma stratified by age, gender and race, we may gain a broader understanding of glaucoma pathogenesis and derive individualised treatment strategies.

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Impact of combination of local carbonic anhydrase inhibitors and beta-blockers on intraocular pressure, visual functions and eye hemodynamics in primary open-angle glaucoma

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2021-14-2-96-102 ◽

2021 ◽

Vol 14 (2) ◽

pp. 96-102

Author(s):

T. N. Malishevskaya ◽

T. N. Kiseleva ◽

A. S. Vlasova ◽

E. K. Eliseeva

Keyword(s):

Blood Flow ◽

Intraocular Pressure ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Beta Blockers ◽

Visual Fields ◽

Significant Risk ◽

Open Angle ◽

Treatment Optimization ◽

Visual Functions

Drug treatment optimization in primary open-angle glaucoma (POAG) is a topical issue of ophthalmology in recent decades. The review focuses on the choice of local hypotensive therapy and the effectiveness of a fixed combination (FC) of dorzolamide / timolol in glaucoma treatment. Since decreased perfusion eye pressure and disturbed regulation of local hemodynamics affect the development and progression of glaucomatous optical neuropathy, the use of anti-glaucomatous drugs or other hypotensive agents requires taking account of their effect on intraocular pressure (IOP), visual functions, and ocular blood flow. Most studies show that the hypotensive and hemodynamic effects of dorzolamide/timolol FC contribute to the preservation of visual fields in POAG patients by reducing significant risk factors for POAG progression, such as increased IOP and blood flow deficiency in the retinal and choroidal vessels. Improved hemodynamic parametersdue to local hypotensive treatment can be considered as basis for visual function stabilization, especially in long-term chronic courses of the disease.

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Primary open-angle glaucoma in patients of Middle Eastern descent

Saudi Journal of Ophthalmology ◽

10.1016/j.sjopt.2017.11.004 ◽

2017 ◽

Vol 31 (4) ◽

pp. 209-210 ◽

Cited By ~ 1

Author(s):

Loor Alshawa ◽

Alon Harris ◽

Josh Gross ◽

Alex Snyder ◽

Ambika Rao ◽

...

Keyword(s):

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Middle Eastern ◽

Open Angle

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Association of IL-10 gene promoter polymorphisms with susceptibility to pseudoexfoliation syndrome, pseudoexfoliative and primary open-angle glaucoma

10.21203/rs.2.15510/v2 ◽

2020 ◽

Author(s):

Ghasem Fakhraie ◽

Farshid Parvini ◽

Jalaledin Ghanavi ◽

Shima Saif ◽

poopak farnia

Keyword(s):

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Gene Promoter ◽

Interleukin 10 ◽

Iranian Population ◽

Pseudoexfoliation Syndrome ◽

Genotype Distribution ◽

Open Angle ◽

Promoter Polymorphisms ◽

Significant Difference

Abstract Background: The involvement of cytokines in pathogenesis of pseudoexfoliation syndrome and glaucoma has been demonstrated in several studies. The aim of the present study was to explore the association between three promoter polymorphisms -592C/A (rs1800872), -819C/T (rs1800871) and -1082A/G (rs1800896) of interleukin 10 (IL-10) gene with susceptibility to pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG). Methods: In this study, 114 PEX, 118 PEXG, 114 POAG patients and 126 healthy individuals from Iranian population were participated. Detailed ophthalmic examinations by an ophthalmologist including slit-lamp bio-microscopic examination, dilated examination of the lens, gonioscopy, and funduscopy were carried out on patients and controls. Genomic DNA was extracted from the blood samples and ARMS–PCR was performed to detect promoter polymorphisms of IL-10. Results: In all three SNPs studied, there was a significant difference in the genotype distribution between patients and control subjects. Results revealed that the AA genotype of IL-10 -592C/A SNP is associated with PEX. However, TT genotype of -819C/T and AA genotype of -1082A/G SNP are significantly associated with susceptibility to either PEX or PEXG and POAG disorders. Furthermore, the ACC haplotype containing the IL-10 -1082A allele was associated with PEX ( P = 0.02, OR = 5.76, 95 % CI = 5.17-24.49), PEXG ( P = 0.006, OR = 7.54, 95 % CI = 6.62-30.76) and POAG ( P = 0.003, OR = 8.11, 95 % CI = 7.13-33.15). Conclusions: Our results demonstrated that IL-10 gene promoter polymorphisms are associated with susceptibility to PEX, PEXG and POAG in Iranian population. Considering the fact that IL-10 polymorphisms are associated with various IL-10 expressions, further research is needed to explain its involvement in these disorders and the formation of extracellular fibrillar amyloid deposits in PEX and PEXG.

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Association of IL-10 gene promoter polymorphisms with susceptibility to pseudoexfoliation syndrome, pseudoexfoliative and primary open-angle glaucoma

10.21203/rs.2.15510/v1 ◽

2019 ◽

Author(s):

Ghasem Fakhraie ◽

Farshid Parvini ◽

Jalaledin Ghanavi ◽

Shima Saif ◽

Poopak Farnia

Keyword(s):

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Gene Promoter ◽

Interleukin 10 ◽

Pseudoexfoliation Syndrome ◽

Genotype Distribution ◽

Open Angle ◽

Promoter Polymorphisms ◽

Amyloid Deposits ◽

Significant Difference

Abstract Background: The involvement of cytokines in pathogenesis of pseudoexfoliation syndrome and glaucoma has been demonstrated in several studies. The aim of the present study was to explore the association between three promoter polymorphisms -592C/A (rs1800872), -819C/T (rs1800871) and -1082A/G (rs1800896) of interleukin 10 (IL-10) gene promoter with susceptibility to pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG). Results: In all three SNPs studied, there was a significant difference in the genotype distribution between patients and control subjects. Results revealed that the AA genotype of IL-10 -592C/A SNP is associated with PEX. However, TT genotype of -819C/T and AA genotype of -1082A/G SNP are significantly associated with susceptibility to either PEX or PEXG and POAG disorders. Furthermore, the ACC haplotype containing the IL-10 -1082A allele was associated with PEX, PEXG and POAG. Conclusions: Our results demonstrated that IL-10 gene promoter polymorphisms are associated with susceptibility to PEX, PEXG and POAG in Iranian population. Considering the fact that IL-10 polymorphisms are associated with various IL-10 expressions, further research is needed to explain its involvement in these disorders and the formation of extracellular fibrillar amyloid deposits in PEX and PEXG.

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Lack of Association Between Polymorphisms in TXNRD2 and LMX1B and Primary Open-Angle Glaucoma in a Saudi Cohort

Frontiers in Genetics ◽

10.3389/fgene.2021.690780 ◽

2021 ◽

Vol 12 ◽

Author(s):

Altaf A. Kondkar ◽

Taif A. Azad ◽

Abdullah S. Alobaidan ◽

Tahira Sultan ◽

Essam A. Osman ◽

...

Keyword(s):

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Statistical Tests ◽

Statistical Significance ◽

Middle Eastern ◽

Nucleotide Polymorphisms ◽

Open Angle ◽

Retrospective Case ◽

Genotype Effect ◽

Clinical Indices

Objective: Recent studies have demonstrated an association of single nucleotide polymorphisms (SNPs) rs35934224 in TXNRD2 and rs6478746 near LMX1B genes in primary open-angle glaucoma (POAG) among Europeans. We performed a retrospective, case-control study to investigate the association between the rs35934224 (TXNRD2) and rs6478746 (LMX1B) and POAG in a middle-eastern population from Saudi Arabia.Methods: DNA from 399 participants consisting of 150 POAG cases (83 males and 67 females) and 249 controls (135 males and 114 females) were genotyped using TaqMan® real-time PCR. Statistical tests were performed to evaluate genetic association with POAG and related clinical indices.Results: The minor allele frequency (MAF) of rs35934224[T] was 0.19 and 0.20 in POAG and controls, respectively. The difference was non-significant (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.75–1.55, p = 0.663). Likewise, rs6478746[G] MAF was 0.12 in both cases and controls with no statistical significance (OR = 1.02, 95% CI = 0.67–1.56, p = 0.910). Genotype analysis showed no association with POAG for both the SNPs in combined and gender-stratified groups. Regression analysis showed no significant effect of risk factors such as age, sex, rs35934224, and rs6478746 genotypes on POAG outcome. Furthermore, both the SNPs showed no significant genotype effect on clinical indices such as intraocular pressure (IOP) and cup/disc ratio in POAG patients.Conclusions: Rs35934224 in TXNRD2 and rs6478746 near LMX1B genes are not associated with POAG or related clinical indices such as IOP and cup/disc ratio in a Saudi cohort. Since the study is limited by sample size further investigations are needed to confirm these results in a larger cohort.

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TNF-α Gene Polymorphisms and Primary Open Angle Glaucoma in Romanian Population / Polimorfisme ale genei TNF-α în populația română cu glaucom primar cu unghi deschis

Revista Romana de Medicina de Laborator ◽

10.1515/rrlm-2015-0004 ◽

2015 ◽

Vol 23 (1) ◽

Author(s):

Ruxandra Simionescu ◽

Alina Popa Cherecheanu ◽

Liliana Voinea ◽

Roxana Sfrenț-Cornățeanu

Keyword(s):

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Corneal Thickness ◽

Asian Population ◽

P Value ◽

Genotype Distribution ◽

Nucleotide Polymorphisms ◽

Open Angle ◽

Tnf Α ◽

Romanian Population

AbstractPrimary open-angle glaucoma (POAG) represents the most common form of a heterogeneous group of glaucomatous optic neuropathies which are a worldwide cause of irreversible blindness. Immune dysregulation and the genetic background are considered important risk factors. The influence on susceptibility to POAG of single nucleotide polymorphisms (SNPs) of tumor necrosis factor-α (TNF-α) was intensively studied, mostly on Asian population. We investigated the possible association of two TNF-α SNPs (-308G/A and -857C/T) with susceptibility to POAG and its clinical characteristics. A case-control association study of aforementioned TNF-α SNPs was performed on 197 POAG patients (divided into two subgroups: high-tension and normal-tension glaucoma - HTG/ NTG) versus 208 ethnically matched controls. This is the first study performed on Romanian population. No significant differences were found in terms of allelic frequencies, genotype distribution of the studied SNPs, or their haplotypes between POAG and healthy control groups. In the subgroup analysis, TT genotype of TNF-α -857T-allele was found to be associated with higher values of central corneal thickness (CCT) in NTG subgroup (p-value 0.032). In order to confirm the association between -857C/T SNP of TNF-α and CCT in NTG subgroup of POAG patients, additional studies on different populations should be performed.

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Clinical efficacy of osteopathic correction in the complex treatment of patients with unoperated open-angle glaucoma

Russian Osteopathic Journal ◽

10.32885/2220-0975-2019-3-4-97-105 ◽

2020 ◽

pp. 97-105

Author(s):

E. N. Simakova ◽

O. V. Stenkova

Keyword(s):

Intraocular Pressure ◽

Drug Therapy ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Randomized Study ◽

Main Group ◽

Control Group ◽

Open Angle ◽

Complex Treatment ◽

Hypotensive Drug

Introduction. Glaucoma is one of the most significant eye diseases. It is often diagnosed, not always amenable to therapy, and can lead to a complete loss of visual functions. In recent years, the method of osteopathic correction has become widespread as one of the effective methods of treatment and rehabilitation of patients with pathologies of various body systems. In the pathogenesis of glaucoma, it is customary to distinguish a dystrophic concept, which considers primary open-angle glaucoma as a result of dystrophic changes in the connective tissue, as well as in the endothelial lining of the trabeculae and Schlemm′s canal, especially destructive changes in mitochondria and the alteration of their functional activity. A vascular concept is also distinguished. According to this concept, the central link in the pathogenesis of glaucoma is circulatory disorder in the ciliary vessels, ocular artery, and major vessels of the head and neck, it can be assumed that osteopathic correction in the treatment of patients with open-angle glaucoma will be pathogenetically substantiated and will have a positive effect on intraocular pressure and trophicity of the optic nerve. The goal of research — to study the influence of in osteopathic correction on the nature of unoperated glaucoma (stage IIA) and to substantiate the possibility of using osteopathic correction in the complex treatment of patients with this pathology.Materials and methods. A prospective controlled randomized study was conducted at 52 city polyclinics, branch 3, Moscow, from January 2018 to January 2019. 40 patients (70 eyes) aged 50 to 75 years with primary open-angle glaucoma IIA stage were examined. At this stage of the disease, patients most often seek medical care and the issue of conservative management is primarily considered. All patients were divided into two groups of 20 people: the main group and the control group. The treatment in the main group included hypotensive drug therapy and osteopathic correction. Patients of the control group received only drug therapy. All patients underwent ophthalmic (visometry, tonometry, perimetry) and osteopathic examination twice: before the treatment and after 3 months.Results. For patients with primary open-angle IIA non-operated glaucoma, regional (most often regions of the head, neck, dura mater) and local (abdominal diaphragm, iliac bones, hip and knee joints) somatic dysfunctions were the most typical. In the main group a statistically significant decrease in the frequency and severity of dysfunctions at all levels was stated. Also, in patients receiving osteopathic correction, a significant decrease in the level of intraocular pressure and perimetric indices was noted. In patients of the control group, no reliable changes in these indicators were obtained.Conclusion. The results obtained indicate that osteopathic correction is clinically effective in the complex treatment of patients with primary open-angle II A glaucoma.

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