The association between <i>SIX6</i> gene rs10483727 polymorphism and primary open angle glaucoma: a meta-analysis and TSA_Chinese Journal of Evidence-Based Medicine

Authors：

LI Rui , SUN Jinfang ,  YU Xiaojin , WANG Lina

Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, 210009, P.R.China;

Corresponding author：

YU Xiaojin, Email: xiaojinyu@seu.edu.cn

Keywords：

SIX6; Primary open angle glaucoma; Case-control study; Meta-analysis; Trial sequential analysis (TSA)

DOI：

10.7507/1672-2531.201810069

Video：

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Objectives To systematically review the association between the SIX6 gene rs10483727 mutation and primary open angle glaucoma (POAG).Methods PubMed, Web of Science, The Cochrane Library, CNKI, WanFang Data and VIP databases were searched to collect case-control studies on the SIX6 gene rs10483727 polymorphism and primary open angle glaucoma from inception to December 28^th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed by Stata 12.0 software.Results Seventeen case-control studies in 16 papers were included, involving 9 886 patients and 19 663 controls. The results of meta-analysis showed that rs10483727 polymorphism in SIX6 gene was associated with the risk of POAG in the Asians and Caucasians. However, no association was found in the Africans.Conclusions The current evidence shows that rs10483727 polymorphism in SIX6 gene is associated with the risk of POAG in the Asians and Caucasians.

Citation： LI Rui, SUN Jinfang, YU Xiaojin, WANG Lina. The association between SIX6 gene rs10483727 polymorphism and primary open angle glaucoma: a meta-analysis and TSA. Chinese Journal of Evidence-Based Medicine, 2019, 19(3): 310-317. doi: 10.7507/1672-2531.201810069 Copy

1.	Maggio F. Glaucomas. Top Companion Anim Med, 2015, 30(3): 86-96.
2.	Quigley HA. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006, 90(3): 262-267.
3.	Kothari R, Bokariya P, Singh R, et al. Correlation of pattern reversal visual evoked potential parameters with the pattern standard deviation in primary open angle glaucoma. Int J Ophthalmol, 2014, 7(2): 326-329.
4.	Choi J, Kook MS. Systemic and ocular hemodynamic risk factors in Glaucoma. Biomed Res Int, 2015, 2015: 1-9.
5.	Liu Y, Allingham R. Molecular genetics in glaucoma. Exp Eye Res, 2011, 93(4): 331-339.
6.	Wiggs JL, Pasquale LR. Genetics of glaucoma. Hum Mol Genet, 2017, 26(R1): R21-R27.
7.	Lascaratos G, Garway-Heath DF, Willoughby CE, et al. Mitochondrial dysfunction in glaucoma: Understanding genetic influences. Mitochondrion, 2012, 12(2): 202-212.
8.	Kawakami K, Sato S, Ozaki H, et al. Six family genes-structure and function as transcription factors and their roles in development. Bioessays, 2000, 22(7): 616-26.
9.	Gallardo ME, Lopez-Rios J, Fernaud-Espinosa I, et al. Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and Associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies. Genomics, 1999, 61(1): 82-91.
10.	Chen Y, Hughes G, Chen X, et al. Genetic variants associated with different risks for high tension glaucoma and normal tension glaucoma in a Chinese population. Invest Ophthalmol Vis Sci, 2015, 56(4): 2595.
11.	Iglesias AI, Springelkamp H, van der Linde H, et al. Exome sequencing and functional analyses suggest that SIX6 is a gene involved in an altered proliferation–differentiation balance early in life and optic nerve degeneration at old age. Hum Mol Genet, 2014, 23(5): 1320-1332.
12.	Aijaz S, Allen J, Tregidgo R, et al. Expression analysis of SIX3 and SIX6 in human tissues reveals differences in expression and a novel correlation between the expression of SIX3 and the genes encoding isocitrate dehyhrogenase and cadherin 18. Genomics, 2005, 86(1): 86-99.
13.	Li X, Perissi V, Liu F, et al. Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science, 2002, 297(5584): 1180-1183.
14.	Osman W, Low S, Takahashi A, et al. A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. Hum Mol Genet, 2012, 21(12): 2836-2842.
15.	Sang J, Jia L, Zhao B, et al. Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population. Sci China Life Sci, 2016, 59(7): 694-699.
16.	Micheal S, Ayub H, Khan MI, et al. Association of known common genetic variants with primary open angle, primary angle closure, and pseudoexfoliation glaucoma in Pakistani cohorts. Mol Vis, 2014, 20: 1471-1479.
17.	Mohd HS, Noemi T, Subbaiah RK, et al. Identification and characterization of variants and a novel 4 bp deletion in the regulatory region of SIX6, a risk factor for primary open-angle glaucoma. Mol Genet Genomic Med, 2017, 5(4): 323-335.
18.	Torlund K, Engstrøm J, Wetterslev J, et al. User manual for trial sequential analysis (TSA). Copenhagen Trial Unit. Available at: http://wwwctudk/tsa/fles/tsa_manualpdf.
19.	Hartling L, Milne A, Hamm MP, et al. Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers. J Clin Epidemiol, 2013, 66(9): 982-993.
20.	Brok J, Thorlund K, Wetterslev J, et al. Apparently conclusive meta-analyses may be inconclusive—Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol, 2009, 38(1): 287-298.
21.	Altaf K, Azad TA, Almobarak FA, et al. Polymorphism rs10483727 in the SIX1/SIX6 gene locus is a risk factor for primary open angle glaucoma in a saudi cohort. Genet Test Mol Biomarkers, 2018, 22(1): 74-78.
22.	辛向阳, 陈鹏, 刘晨璐. 视盘相关基因多态性与内蒙古自治区原发性开角型青光眼易感性的关系. 中华实验眼科杂志, 2018, 36(4): 279-283.
23.	Munemitsu Y, Nakanishi H, Yamashiro K, et al. Association of glaucoma-susceptible genes to regional circumpapillary retinal nerve fiber layer thickness and visual field defects. Invest Ophthalmol Vis Sci, 2017, 58(5): 2510-2519.
24.	Fan BJ, Wang DY, Pasquale LR, et al. Genetic variants associated with optic nerve vertical cup-to-disc ratio are risk factors for primary open angle glaucoma in a US Caucasian population. Invest Ophthalmol Vis Sci, 2011, 52(3): 1788.
25.	Mabuchi F, Sakurada Y, Kashiwagi K, et al. Association between genetic variants associated with vertical cup-to-disc ratio and phenotypic features of primary open-angle glaucoma. Ophthalmology, 2012, 119(9): 1819-1825.
26.	Dimasi DP, Burdon KP, Hewitt AW, et al. Genetic investigation into the endophenotypic status of central corneal thickness and optic disc parameters in relation to open-angle glaucoma. Am J Ophthalmol, 2012, 154(5): 833-842.
27.	Cao D, Jiao X, Liu X, et al. CDKN2B polymorphism is associated with primary open-angle glaucoma (POAG) in the Afro-Caribbean population of Barbados, west Indies. PLoS One, 2012, 7(6): e39278.
28.	Burdon KP, Mitchell P, Lee A, et al. Association of open-angle glaucoma loci with incident glaucoma in the blue mountains eye study. Am J Ophthalmol, 2015, 159(1): 31-36.
29.	Wiggs JL, Yaspan BL, Hauser MA, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genet, 2012, 8(4): e1002654.
30.	Liu Y, Hauser MA, Akafo SK, et al. Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry. Invest Ophthalmol Vis Sci, 2013, 54(9): 6248-54.
31.	Williams SEI, Carmichael TR, Allingham RR, et al. The genetics of POAG in black south Africans: a Candidate gene association study. Sci Rep, 2015, 5: 8378.
32.	Wang X, Harmon J, Zabrieskie N, et al. Using the utah population database to assess familial risk of primary open angle glaucoma. Vision Res, 2010, 50(1): 2391-2395.
33.	Van Koolwijk LM, Despriet DD, Van Duijn CM, et al. Genetic contributions to glaucoma: heritability of intraocular pressure, retinal nerve fiber layer thickness, and optic disc morphology. Invest Ophthalmol Vis Sci, 2007, 48(8): 3669-3676.
34.	Cornelis MC, Agrawal A, Cole JW, et al. The gene, environment association studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions. Genet Epidemiol, 2010, 34(4): 364-372.
35.	Burdon KP, Macgregor S, Hewitt AW, et al. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet, 2011, 43(1): 574-578.
36.	Thorleifsson G, Walters GB, Hewitt AW, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet, 2010, 42(1): 906-909.
37.	Springelkamp H, Hohn R, Mishra A, et al. meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun, 2014, 5(1): 4883.
38.	Junoy Montolio FG, Wesselink C, Gordijn M, et al. Factors that influence standard automated perimetry test results in glaucoma: test reliability, technician experience, time of day, and season. Invest Ophthalmol Vis Sci, 2012, 53(1): 7010-7017.

1. Maggio F. Glaucomas. Top Companion Anim Med, 2015, 30(3): 86-96.
2. Quigley HA. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006, 90(3): 262-267.
3. Kothari R, Bokariya P, Singh R, et al. Correlation of pattern reversal visual evoked potential parameters with the pattern standard deviation in primary open angle glaucoma. Int J Ophthalmol, 2014, 7(2): 326-329.
4. Choi J, Kook MS. Systemic and ocular hemodynamic risk factors in Glaucoma. Biomed Res Int, 2015, 2015: 1-9.
5. Liu Y, Allingham R. Molecular genetics in glaucoma. Exp Eye Res, 2011, 93(4): 331-339.
6. Wiggs JL, Pasquale LR. Genetics of glaucoma. Hum Mol Genet, 2017, 26(R1): R21-R27.
7. Lascaratos G, Garway-Heath DF, Willoughby CE, et al. Mitochondrial dysfunction in glaucoma: Understanding genetic influences. Mitochondrion, 2012, 12(2): 202-212.
8. Kawakami K, Sato S, Ozaki H, et al. Six family genes-structure and function as transcription factors and their roles in development. Bioessays, 2000, 22(7): 616-26.
9. Gallardo ME, Lopez-Rios J, Fernaud-Espinosa I, et al. Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and Associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies. Genomics, 1999, 61(1): 82-91.
10. Chen Y, Hughes G, Chen X, et al. Genetic variants associated with different risks for high tension glaucoma and normal tension glaucoma in a Chinese population. Invest Ophthalmol Vis Sci, 2015, 56(4): 2595.
11. Iglesias AI, Springelkamp H, van der Linde H, et al. Exome sequencing and functional analyses suggest that SIX6 is a gene involved in an altered proliferation–differentiation balance early in life and optic nerve degeneration at old age. Hum Mol Genet, 2014, 23(5): 1320-1332.
12. Aijaz S, Allen J, Tregidgo R, et al. Expression analysis of SIX3 and SIX6 in human tissues reveals differences in expression and a novel correlation between the expression of SIX3 and the genes encoding isocitrate dehyhrogenase and cadherin 18. Genomics, 2005, 86(1): 86-99.
13. Li X, Perissi V, Liu F, et al. Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science, 2002, 297(5584): 1180-1183.
14. Osman W, Low S, Takahashi A, et al. A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. Hum Mol Genet, 2012, 21(12): 2836-2842.
15. Sang J, Jia L, Zhao B, et al. Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population. Sci China Life Sci, 2016, 59(7): 694-699.
16. Micheal S, Ayub H, Khan MI, et al. Association of known common genetic variants with primary open angle, primary angle closure, and pseudoexfoliation glaucoma in Pakistani cohorts. Mol Vis, 2014, 20: 1471-1479.
17. Mohd HS, Noemi T, Subbaiah RK, et al. Identification and characterization of variants and a novel 4 bp deletion in the regulatory region of SIX6, a risk factor for primary open-angle glaucoma. Mol Genet Genomic Med, 2017, 5(4): 323-335.
18. Torlund K, Engstrøm J, Wetterslev J, et al. User manual for trial sequential analysis (TSA). Copenhagen Trial Unit. Available at: http://wwwctudk/tsa/fles/tsa_manualpdf.
19. Hartling L, Milne A, Hamm MP, et al. Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers. J Clin Epidemiol, 2013, 66(9): 982-993.
20. Brok J, Thorlund K, Wetterslev J, et al. Apparently conclusive meta-analyses may be inconclusive—Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol, 2009, 38(1): 287-298.
21. Altaf K, Azad TA, Almobarak FA, et al. Polymorphism rs10483727 in the SIX1/SIX6 gene locus is a risk factor for primary open angle glaucoma in a saudi cohort. Genet Test Mol Biomarkers, 2018, 22(1): 74-78.
22. 辛向阳, 陈鹏, 刘晨璐. 视盘相关基因多态性与内蒙古自治区原发性开角型青光眼易感性的关系. 中华实验眼科杂志, 2018, 36(4): 279-283.
23. Munemitsu Y, Nakanishi H, Yamashiro K, et al. Association of glaucoma-susceptible genes to regional circumpapillary retinal nerve fiber layer thickness and visual field defects. Invest Ophthalmol Vis Sci, 2017, 58(5): 2510-2519.
24. Fan BJ, Wang DY, Pasquale LR, et al. Genetic variants associated with optic nerve vertical cup-to-disc ratio are risk factors for primary open angle glaucoma in a US Caucasian population. Invest Ophthalmol Vis Sci, 2011, 52(3): 1788.
25. Mabuchi F, Sakurada Y, Kashiwagi K, et al. Association between genetic variants associated with vertical cup-to-disc ratio and phenotypic features of primary open-angle glaucoma. Ophthalmology, 2012, 119(9): 1819-1825.
26. Dimasi DP, Burdon KP, Hewitt AW, et al. Genetic investigation into the endophenotypic status of central corneal thickness and optic disc parameters in relation to open-angle glaucoma. Am J Ophthalmol, 2012, 154(5): 833-842.
27. Cao D, Jiao X, Liu X, et al. CDKN2B polymorphism is associated with primary open-angle glaucoma (POAG) in the Afro-Caribbean population of Barbados, west Indies. PLoS One, 2012, 7(6): e39278.
28. Burdon KP, Mitchell P, Lee A, et al. Association of open-angle glaucoma loci with incident glaucoma in the blue mountains eye study. Am J Ophthalmol, 2015, 159(1): 31-36.
29. Wiggs JL, Yaspan BL, Hauser MA, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genet, 2012, 8(4): e1002654.
30. Liu Y, Hauser MA, Akafo SK, et al. Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry. Invest Ophthalmol Vis Sci, 2013, 54(9): 6248-54.
31. Williams SEI, Carmichael TR, Allingham RR, et al. The genetics of POAG in black south Africans: a Candidate gene association study. Sci Rep, 2015, 5: 8378.
32. Wang X, Harmon J, Zabrieskie N, et al. Using the utah population database to assess familial risk of primary open angle glaucoma. Vision Res, 2010, 50(1): 2391-2395.
33. Van Koolwijk LM, Despriet DD, Van Duijn CM, et al. Genetic contributions to glaucoma: heritability of intraocular pressure, retinal nerve fiber layer thickness, and optic disc morphology. Invest Ophthalmol Vis Sci, 2007, 48(8): 3669-3676.
34. Cornelis MC, Agrawal A, Cole JW, et al. The gene, environment association studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditions. Genet Epidemiol, 2010, 34(4): 364-372.
35. Burdon KP, Macgregor S, Hewitt AW, et al. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet, 2011, 43(1): 574-578.
36. Thorleifsson G, Walters GB, Hewitt AW, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet, 2010, 42(1): 906-909.
37. Springelkamp H, Hohn R, Mishra A, et al. meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun, 2014, 5(1): 4883.
38. Junoy Montolio FG, Wesselink C, Gordijn M, et al. Factors that influence standard automated perimetry test results in glaucoma: test reliability, technician experience, time of day, and season. Invest Ophthalmol Vis Sci, 2012, 53(1): 7010-7017.

Chinese Journal of Evidence-Based Medicine

The association between SIX6 gene rs10483727 polymorphism and primary open angle glaucoma: a meta-analysis and TSA

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