Association of WDR36 polymorphisms with primary open-angle glaucoma
Medical hypothesis, discovery & innovation in optometry,
Vol. 4 No. 4 (2023),
25 December 2023
,
Page 174-180
https://doi.org/10.51329/mehdioptometry188
Abstract
Background: Various genes contribute to the pathophysiology of primary open-angle glaucoma (POAG). The WD repeat domain 36 (WDR36) gene may participate in T cell activation and, hence, in the pathogenesis of POAG. We investigated the association of two WDR36 gene single nucleotide polymorphisms (SNPs) with POAG.Methods: This cross-sectional study recruited patients aged >40 years with POAG and investigated the rs10038177 and rs1971050 SNPs of WDR36 using polymerase chain reaction and direct DNA sequencing. All participants underwent comprehensive ocular examination, visual field assessment using the Swedish Interactive Threshold Algorithm standard 24-2 threshold test, and measurement of peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography.
Results: We enrolled 105 patients with a mean (standard deviation) age of 55.41 (8.56) years and a male-to-female ratio of 56 (53.3%) to 49 (46.7%), most of whom had a diagnosis of POAG for 2 to 5 years (60.0%). Most participants had diabetes (90.5%) but not hypertension (88.6%). There was a significant association of rs10038177 (P<0.05), but not rs1971050 (P>0.05), with family history of glaucoma. The association between rs10038177 and intraocular pressure was significant (P<0.05), but that between rs1971050 and intraocular pressure was not (P>0.05). No significant association was observed between mean cup-to-disc ratio and either SNP (both P>0.05). For rs10038177, a significant association was found only with the RNFLT of the superior quadrant (P<0.05), whereas for rs1971050, a significant association was found with the RNFLT of all four quadrants and average RNFLT (all P<0.05). However, pairwise comparisons revealed no significant differences between genotypes (P>0.05 for all pairwise comparisons). The association of rs10038177 with glaucoma severity was insignificant (P>0.05), and most patients with the TC genotype (71.7%) had moderate severity. There was no significant association between rs1971050 and glaucoma severity (P>0.05).
Conclusions: We observed genetic links between some, but not all, characteristics of POAG and the rs10038177 and rs1971050 SNPs of WDR36. Follow-up studies on these and other WDR36 SNPs in populations with different genetic backgrounds are necessary to confirm this genetic association.
Keywords:
- glaucomas
- primary open angle glaucoma
- WD repeat-containing protein 36
- genetic polymorphism
- single nucleotide polymorphism
- optical coherence tomography
- family medical history
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22. Permenter J, Ishwar A, Rounsavall A, Smith M, Faske J, Sailey CJ, et al. Quantitative analysis of genomic DNA degradation in whole blood under various storage conditions for molecular diagnostic testing. Mol Cell Probes. 2015;29(6):449-453. doi: 10.1016/j.mcp.2015.07.002 pmid: 26166695
23. Malik M, Khan T, Singh L, Raza T, Shahaan S. Association of rs 10038177 and rs 1971050 Polymorphism of WDR 36 Gene with Clinical Profile in POAG Patients. Modern Medicine. 2021;28(4): 427-433. doi: 10.31689/rmm.2021.28.4.433
24. Fuse N. Genetic bases for glaucoma. Tohoku J Exp Med. 2010;221(1):1-10. doi: 10.1620/tjem.221.1 pmid: 20431268
25. Janssen SF, Gorgels TG, Ramdas WD, Klaver CC, van Duijn CM, Jansonius NM, et al. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog Retin Eye Res. 2013;37:31-67. doi: 10.1016/j.preteyeres.2013.09.001 pmid: 24055863
26. Gemenetzi M, Yang Y, Lotery AJ. Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment. Eye (Lond). 2012;26(3):355-69. doi: 10.1038/eye.2011.309 pmid: 22173078
27. Wu J, Du Y, Li J, Fan X, Lin C, Wang N. The influence of different intraocular pressure on lamina cribrosa parameters in glaucoma and the relation clinical implication. Sci Rep. 2021;11(1):9755. doi: 10.1038/s41598-021-87844-1 pmid: 33963202
28. Swaminathan SS, Jammal AA, Berchuck SI, Medeiros FA. Rapid initial OCT RNFL thinning is predictive of faster visual field loss during extended follow-up in glaucoma. Am J Ophthalmol. 2021;229:100-107. doi: 10.1016/j.ajo.2021.03.019 pmid: 33775658
29. Su HA, Li SY, Yang JJ, Yen YC. An Application of NGS for WDR36 Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma. Int J Med Sci. 2017;14(12):1251-1256. doi: 10.7150/ijms.20729 pmid: 29104481
30. Mookherjee S, Chakraborty S, Vishal M, Banerjee D, Sen A, Ray K. WDR36 variants in East Indian primary open-angle glaucoma patients. Mol Vis. 2011;17:2618-27. pmid: 22025897
2. Kim KE, Park KH. Update on the Prevalence, Etiology, Diagnosis, and Monitoring of Normal-Tension Glaucoma. Asia Pac J Ophthalmol (Phila). 2016;5(1):23-31. doi: 10.1097/APO.0000000000000177 pmid: 26886116
3. Lee SS, Mackey DA. Glaucoma - risk factors and current challenges in the diagnosis of a leading cause of visual impairment. Maturitas. 2022;163:15-22. doi: 10.1016/j.maturitas.2022.05.002 pmid: 35597227
4. Grzybowski A, Och M, Kanclerz P, Leffler C, Moraes CG. Primary Open Angle Glaucoma and Vascular Risk Factors: A Review of Population Based Studies from 1990 to 2019. J Clin Med. 2020;9(3):761. doi: 10.3390/jcm9030761 pmid: 32168880
5. Al-Namaeh M. Pharmaceutical treatment of primary open angle glaucoma. Med Hypothesis Discov Innov Optom. 2021; 2(1): 8-17. doi: 10.51329/mehdioptometry120
6. Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol. 2016;100(1):86-93. doi: 10.1136/bjophthalmol-2015-307223 pmid: 26286821
7. Rashidian P. Race in the phenotype of glaucoma: genotypic or environmental variance? Med Hypothesis Discov Innov Optom. 2021; 2(4): 161-162. doi: 10.51329/mehdioptometry142
8. Fingert JH. Primary open-angle glaucoma genes. Eye (Lond). 2011;25(5):587-95. doi: 10.1038/eye.2011.97 pmid: 21562585
9. Liu Y, Allingham RR. Major review: Molecular genetics of primary open-angle glaucoma. Exp Eye Res. 2017;160:62-84. doi: 10.1016/j.exer.2017.05.002 pmid: 28499933
10. Saglar E, Yucel D, Bozkurt B, Ozgul RK, Irkec M, Ogus A. Association of polymorphisms in APOE, p53, and p21 with primary open-angle glaucoma in Turkish patients. Mol Vis. 2009;15:1270-6 pmid: 19578553
11. Monemi S, Spaeth G, DaSilva A, Popinchalk S, Ilitchev E, Liebmann J, et al. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1. Hum Mol Genet. 2005;14(6):725-33. doi: 10.1093/hmg/ddi068 pmid: 15677485
12. Mao M, Biery MC, Kobayashi SV, Ward T, Schimmack G, Burchard J, et al. T lymphocyte activation gene identification by coregulated expression on DNA microarrays. Genomics. 2004;83(6):989-99. doi: 10.1016/j.ygeno.2003.12.019 pmid: 15177553
13. Liu K, He W, Zhao J, Zeng Y, Cheng H. Association of WDR36 polymorphisms with primary open angle glaucoma: A systematic review and meta-analysis. Medicine (Baltimore). 2017;96(26):e7291. doi: 10.1097/MD.0000000000007291 pmid: 28658128
14. Taher AA, Mohmmad HJ, Hussain MK, Al-Talqani HM. Two Variants of WDR36 Genes on primary open angle glaucoma. EC Ophthalmology. 2016;3:352-8. Link
15. Blanco-Marchite C, Sánchez-Sánchez F, López-Garrido MP, Iñigez-de-Onzoño M, López-Martínez F, López-Sánchez E, et al. WDR36 and P53 gene variants and susceptibility to primary open-angle glaucoma: analysis of gene-gene interactions. Invest Ophthalmol Vis Sci. 2011;52(11):8467-78. doi: 10.1167/iovs.11-7489 pmid: 21931130
16. Fan BJ, Wang DY, Cheng CY, Ko WC, Lam SC, Pang CP. Different WDR36 mutation pattern in Chinese patients with primary open-angle glaucoma. Mol Vis. 2009;15:646-53. pmid: 19347049
17. Jia LY, Tam PO, Chiang SW, Ding N, Chen LJ, Yam GH, et al. Multiple gene polymorphisms analysis revealed a different profile of genetic polymorphisms of primary open-angle glaucoma in northern Chinese. Mol Vis. 2009;15:89-98. pmid: 19145250
18. Green CM, Kearns LS, Wu J, Barbour JM, Wilkinson RM, Ring MA, et al. How significant is a family history of glaucoma? Experience from the Glaucoma Inheritance Study in Tasmania. Clin Exp Ophthalmol. 2007;35(9):793-9. doi: 10.1111/j.1442-9071.2007.01612.x pmid: 18173405
19. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):e13-e115. doi: 10.1161/HYP.0000000000000065. Erratum in: Hypertension. 2018;71(6):e140-e144. pmid: 29133356
20. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S14-S31. doi: 10.2337/dc20-S002 pmid: 31862745
21. Brusini P, Johnson CA. Staging functional damage in glaucoma: review of different classification methods. Surv Ophthalmol. 2007;52(2):156-79. doi: 10.1016/j.survophthal.2006.12.008. pmid: 17355855
22. Permenter J, Ishwar A, Rounsavall A, Smith M, Faske J, Sailey CJ, et al. Quantitative analysis of genomic DNA degradation in whole blood under various storage conditions for molecular diagnostic testing. Mol Cell Probes. 2015;29(6):449-453. doi: 10.1016/j.mcp.2015.07.002 pmid: 26166695
23. Malik M, Khan T, Singh L, Raza T, Shahaan S. Association of rs 10038177 and rs 1971050 Polymorphism of WDR 36 Gene with Clinical Profile in POAG Patients. Modern Medicine. 2021;28(4): 427-433. doi: 10.31689/rmm.2021.28.4.433
24. Fuse N. Genetic bases for glaucoma. Tohoku J Exp Med. 2010;221(1):1-10. doi: 10.1620/tjem.221.1 pmid: 20431268
25. Janssen SF, Gorgels TG, Ramdas WD, Klaver CC, van Duijn CM, Jansonius NM, et al. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog Retin Eye Res. 2013;37:31-67. doi: 10.1016/j.preteyeres.2013.09.001 pmid: 24055863
26. Gemenetzi M, Yang Y, Lotery AJ. Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment. Eye (Lond). 2012;26(3):355-69. doi: 10.1038/eye.2011.309 pmid: 22173078
27. Wu J, Du Y, Li J, Fan X, Lin C, Wang N. The influence of different intraocular pressure on lamina cribrosa parameters in glaucoma and the relation clinical implication. Sci Rep. 2021;11(1):9755. doi: 10.1038/s41598-021-87844-1 pmid: 33963202
28. Swaminathan SS, Jammal AA, Berchuck SI, Medeiros FA. Rapid initial OCT RNFL thinning is predictive of faster visual field loss during extended follow-up in glaucoma. Am J Ophthalmol. 2021;229:100-107. doi: 10.1016/j.ajo.2021.03.019 pmid: 33775658
29. Su HA, Li SY, Yang JJ, Yen YC. An Application of NGS for WDR36 Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma. Int J Med Sci. 2017;14(12):1251-1256. doi: 10.7150/ijms.20729 pmid: 29104481
30. Mookherjee S, Chakraborty S, Vishal M, Banerjee D, Sen A, Ray K. WDR36 variants in East Indian primary open-angle glaucoma patients. Mol Vis. 2011;17:2618-27. pmid: 22025897
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