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Biochemical Markers in Ophthalmology
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Abdus Samad Ansari, Pirro G. Hysi
Several GWAS studies that took place between 2010 and 2020 identified several genomic regions that altered susceptibility to POAG [58–61]. Using well-selected clinically diagnosed POAG samples and comparing their genotypes with healthy controls, these studies identified genetic loci that are associated with the highest risk to POAG in general populations. The pathogenetic mechanisms were almost always clear, as the same loci tended to show strong association with glaucoma endophenotypes such as IOP (e.g., TMCO1, CAV1,2, and GAS7 loci) or optic nerve head morphology (CDKN2B-AS1).
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Researchers have also identified a number of genetic biomarkers (i.e., SNPs) associated with gliomas. These include EGFR, ETFA, TP53, TERT, TERC, CDKN2B–AS1, RTEL1, CCDC26, PHLDB1, and POLR3B. Some of these have shown a strong association with the disease, while others have not reached statistical significance. From currently available data on studies involving CTCs, nucleic acids and proteins shed from malignant gliomas, it is unclear which biomarker class or type is the most promising for the future in terms of developing a robust screening assay.
Molecular basis and biomarkers of disease activity
Published in Seema Chopra, Endometriosis, 2020
GWAS has shown a positive association of endometriosis with the SNP rs1096523, which is located in the cyclin-dependent kinase inhibitor 2B antisense RNA (CDKN2BAS) gene on chromosome 9p21. CDKN2BAS regulates the expression of CDKN2A, which controls proliferation of endometrium and is implicated in etiopathogenesis of endometriosis [44]. Additionally, a similar association has been observed with rs16826658m in the linkage disequilibrium block which also includes the gene WNT4 on chromosome 1p36 [44]. WNT4 signaling plays a role in the development of ovarian follicles, fallopian tubes, and the uterus from the Müllerian ducts. An association of endometriosis has also been found with the locus 9p21 that is also associated with other diseases, including malignant melanoma, basal cell carcinoma, coronary artery disease, type 2 diabetes, glioma, and nevi [42]. A few other loci that have been linked to increased susceptibility for endometriosis include 7p15.2 (a region between NFE2L3 and HOXA10) and 10q26. However, the clinical significance of these genetic variants in predicting the risk of the disease is still unclear. Recently, some researchers have demonstrated an increased prevalence of an inherited polymorphism of a let-7 miRNA-binding site in the KRAS gene in patients with endometriosis as the first described genetic marker for endometriosis risk and also a potential therapeutic target [45].
The rs1333040 and rs10757278 9p21 locus polymorphisms in patients with intracranial aneurysm: a meta-analysis
Published in International Journal of Neuroscience, 2023
Antonis Adamou, Georgios Mavrovounis, Eleftherios T. Beltsios, Ioannis Liampas, Zisis Tsouris, Athina-Maria Aloizou, Vasileios Siokas, Efthimios Dardiotis
CDKN2BAS or ANRIL, which stands for ‘antisense noncoding RNA in the INK4 locus’, is a group of multiple linear isoforms encoded in the 9p21 locus. The rs1333040 and rs10757278 polymorphisms are located in the ANRIL genomic region. The ANRIL molecule binds to polycomb protein complexes 1 and 2 (PRC1/PRC2), repressing their action. These complexes are crucial developmental regulators that participate in the silencing of genes associated with cell growth and carcinogenesis, by epigenetic methylation of their neighbor tumor suppressors cyclin-dependent kinase inhibitor 2 A (CDKN2A) and CDKN2B [18]. Therefore, ANRIL interferes with the normal function of PRC1 and 2, presumably promoting carcinogenesis, uncontrolled cell growth and differentiation [19]. The exact mechanism, though, through which ANRIL contributes to the formation of IA is still unclear.
Development and Evaluation of a Rules-based Algorithm for Primary Open-Angle Glaucoma in the VA Million Veteran Program
Published in Ophthalmic Epidemiology, 2022
Cari L. Nealon, Christopher W. Halladay, Tyler G. Kinzy, Piana Simpson, Rachael L. Canania, Scott A. Anthony, David P. Roncone, Lea R. Sawicki Rogers, Jenna N. Leber, Jacquelyn M. Dougherty, Jack M. Sullivan, Wen-Chih Wu, Paul B. Greenberg, Sudha K. Iyengar, Dana C. Crawford, Neal S. Peachey, Jessica N. Cooke Bailey
In this study, we developed and evaluated rules-based algorithms for POAG and deployed them in the nation-wide CPRS to identify cases and controls for downstream genome-wide studies. The accuracy of the final algorithms was comparable at three VAMCECs. The robustness of the algorithms to identify cases and controls for genetic analyses was confirmed by evaluating genetic association at CDKN2BAS-1, an established POAG locus in European-descent populations that has also been suggestively associated with POAG in African-descent populations. Our assumption was that cases would carry more copies of the high risk variant. Because markers at CDKN2BAS-1 have been identified and validated in large studies independent of the MVP, contrasting genetic profiles between cases and controls at this locus enabled us to corroborate the authenticity of the computable phenotype.
The haplotype of the CDKN2B-AS1 gene is associated with primary open-angle glaucoma and pseudoexfoliation glaucoma in the Caucasian population of Central Russia
Published in Ophthalmic Genetics, 2021
Natalya Eliseeva, Irina Ponomarenko, Evgeny Reshetnikov, Volodymyr Dvornyk, Mikhail Churnosov
CDKN2B-AS1 is a pleiotropic gene documented for its potential role in cancer, atherosclerosis, coronary artery disease, type-2 diabetes (41,43,54), and regulatory effect on CDKN2A and CDKN2B (55). In patients with coronary artery disease, overexpression of CDKN2B-AS1 significantly decreased the expression of tumor suppressors CDKN2A and CDKN2B, thus indicating a reciprocal cis-acting regulatory relationship between these three genes (44). Importantly, heart atherosclerosis, heart ischemia, and diabetes are significant factors (p < .001) for the risk of both POAG and PXFG in our study sample. CDKN2B-AS1 may be an important element of the TGFβ1 signaling pathway by blocking the TGFβ1-induced cell cycle inhibition and contributing to the lower expression level of CDKN2B (56). Downregulation of CDKN2B-AS1 was shown to increase cellular senescence, TGFβ signaling, and ECM deposition in TM cells (57). This suggests that neuroinflammation likely contributes to senescence and death of retinal ganglion cells or glia during the pathogenesis of POAG and PXFG. The recent comprehensive bioinformatics analysis of candidate genes for POAG (termed “POAGome”) suggested a key role of the CDKN2B-AS1, CDKN2B, and CDKN2A genes in the POAG-associated network “Free Radical Scavenging, Glomerular Injury, Organismal Injury and Abnormalities” (55).