Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort

Kondkar, Altaf A.; Azad, Taif A.; Sultan, Tahira; Osman, Essam; Almobarak, Faisal A.; Al-Obeidan, Saleh A.

doi:10.1371/journal.pone.0227417

Cited by 18 publications

(17 citation statements)

References 55 publications

(78 reference statements)

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“…Generally, however, follow-up of genetic loci that have been identified in other populations—specifically loci identified in a Japanese population—have led to largely negative associations in ME populations [ 62 , 105 , 106 , 107 , 108 , 109 , 110 , 111 ]. Individual SNPs for other genes, including the SIX1/SIX6 locus and the endothelial nitric oxide synthase gene ( NOS3 ), have been identified as associated with POAG in a Saudi Arabian population [ 63 , 112 ]. Meanwhile, in Iran, an association between POAG and the p53 pro72 allele ( p < 0.05), as well as polymorphisms of the IL-10 gene promoter, have been noted and reflect findings in a Chinese population [ 113 , 114 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

Zukerman

Harris

Vercellin

et al. 2020

Genes

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Glaucoma, the world’s leading cause of irreversible blindness, is a complex disease, with differential presentation as well as ethnic and geographic disparities. The multifactorial nature of glaucoma complicates the study of genetics and genetic involvement in the disease process. This review synthesizes the current literature on glaucoma and genetics, as stratified by glaucoma subtype and ethnicity. Primary open-angle glaucoma (POAG) is the most common cause of glaucoma worldwide, with the only treatable risk factor (RF) being the reduction of intraocular pressure (IOP). Genes associated with elevated IOP or POAG risk include: ABCA1, AFAP1, ARHGEF12, ATXN2, CAV1, CDKN2B-AS1, FOXC1, GAS7, GMDS, SIX1/SIX6, TMCO1, and TXNRD2. However, there are variations in RF and genetic factors based on ethnic and geographic differences; it is clear that unified molecular pathways accounting for POAG pathogenesis remain uncertain, although inflammation and senescence likely play an important role. There are similar ethnic and geographic complexities in primary angle closure glaucoma (PACG), but several genes have been associated with this disorder, including MMP9, HGF, HSP70, MFRP, and eNOS. In exfoliation glaucoma (XFG), genes implicated include LOXL1, CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A. Despite tremendous progress, major gaps remain in resolving the genetic architecture for the various glaucoma subtypes across ancestries. Large scale carefully designed studies are required to advance understanding of genetic loci as RF in glaucoma pathophysiology and to improve diagnosis and treatment options.

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Section: Discussionmentioning

confidence: 99%

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

Zukerman

Harris

Vercellin

et al. 2020

Genes

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“…Alterations in TXNRD2 function may plausibly result in mitochondrial abnormalities and increased oxidative stress. Many studies in the past have implied an essential role of mitochondrial abnormalities and oxidative stress in the pathogenesis of POAG, including patients of Saudi origin (Abu-Amero et al, 2006 , 2013b ; Lascaratos et al, 2012 ; Kondkar et al, 2018c , 2020 ). Likewise, mitochondrial dysfunction has also been implicated in RGC loss in experimental glaucoma models (Osborne, 2008 ; Lascaratos et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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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“…[26][27][28][29][30][31] More recently, Kondkar et al identified several polymorphisms of the endothelial nitric oxide synthase (NOS3) gene that may modify the risk of POAG in the SA population, possibly supporting the oxidative stress hypothesis for the pathogenesis of POAG. [32] Additionally, polymorphism of the SIX1/SIX6 gene locus has been identified in SA (genotype distribution, p = 0.012). [33] Meanwhile in Iran, a cohort study of 65 unrelated patients had a statistically significant increased occurrence of POAG and the p53 Pro72 allele (p < 0.05), [34] and a more recent Iranian study demonstrated that polymorphisms of the IL-10 gene promoter are significantly associated with susceptibility to POAG similar to findings demonstrating IL-10 polymorphisms to be predictive of POAG pathogenesis in China.…”

Section: Chromosomal Influencesmentioning

confidence: 99%

“…Chromosomes O O [32][33][34][35][36] Familial trends O ? Age and gender O O [14,17] Socioeconomic status O O [14,17] Lifestyle O ?…”

Section: Risk Factors Non-middle Eastern Countries Middle Eastern Countriesmentioning

confidence: 99%

Prevalence Rates and Risk Factors for Primary Open Angle Glaucoma in the Middle East

Torabi

Harris

Siesky

et al. 2021

JOVR

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Glaucoma is a multifactorial disease and a leading cause of irreversible blindness worldwide. Current data has demonstrated the approximate distribution of primary openangle glaucoma (POAG) in patients of European, African, Hispanic, and Eastern Asian descent. However, a significant gap in the literature exists regarding the prevalence of POAG in Middle Eastern (ME) populations. Current studies estimate ME POAG prevalence based on a European model. Herein we screened 65 total publications on ME prevalence of POAG and specific risk factors using keywords: “glaucoma”, “prevalence”, “incidence”, “risk factor”, “Middle East”, “Mideast”, “Persian”, “Far East”, as well as searching by individual ME countries through PubMed, Embase, Ovid, Scopus, and Trip searches with additional reference list searches from relevant articles published up to and including March 1, 2021. Fifty qualifying records were included after 15 studies identified with low statistical power, confounding co-morbid ophthalmic diseases, and funding bias were excluded. Studies of ME glaucoma risk factors that identify chromosomes, familial trend, age/gender, socioeconomic status, lifestyle, intraocular pressure, vascular influences, optic disc hemorrhage, cup-to-disc ratio, blood pressure, obstructive sleep apnea, and diabetes mellitus were included in this systematic review. We conclude that the prevalence of POAG in the ME is likely higher than the prevalence rate that European models suggest, with ME specific risk factors likely playing a role. However, these findings are severely limited by the paucity of population-level data in the ME. Well-designed, longitudinal population-based studies with rigorous inclusion and exclusion criteria are ultimately needed to accurately assess the epidemiology and specific mechanistic risk factors of glaucoma in ME populations.

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Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort

Cited by 18 publications

References 55 publications

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

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

Prevalence Rates and Risk Factors for Primary Open Angle Glaucoma in the Middle East

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