早产儿视网膜病变遗传易感性_Chinese Journal of Ocular Fundus Diseases

Authors：

许宇 ,  赵培泉

200092 上海交通大学医学院附属新华医院眼科;

Corresponding author：

赵培泉, Email: zhaopeiquan@126.com

Keywords：

早产儿视网膜病/遗传学; 疾病遗传易感性/遗传学; 突变; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.01.028

Video：

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除早产以及环境因素以外,遗传因素在早产儿视网膜病变(ROP)的发生发展中亦伴有重要角色。大规模基因扫描和检测确定了一些与ROP相关的基因多态性或基因突变,包括Wnt信号通路相关的Norrie病蛋白、卷曲蛋白4、低密度脂蛋白受体相关蛋白5和四旋蛋白12基因的突变,以及血管内皮生长因子基因、胰岛素样生长因子1基因和其他相关生长因子基因的多态性。尽管这些发现为基因因素在ROP发病机制中的作用提供了很多证据和支持,但仍需要来自不同地区大样本量的比较和分析才能得出有意义的结论。此外,还需要借助生物信息学技术和蛋白组学技术进一步明确ROP的发病机制。ROP可能是累及多个基因的疾病,而非仅仅累及单一基因;每个基因可能贡献较小,但累积到一定量后可能就导致最终的临床表型出现。随着遗传学技术的不断进步,再整合生物信息学和蛋白组学技术,相信将来能够为ROP的治疗提供更好的方案。

Citation： 许宇, 赵培泉. 早产儿视网膜病变遗传易感性. Chinese Journal of Ocular Fundus Diseases, 2014, 30(1): 97-100. doi: 10.3760/cma.j.issn.1005-1015.2014.01.028 Copy

1.	Mechoulam H, Pierce EA. Retinopathy of prematurity:molecular pathology and therapeutic strategies[J]. Am J Pharmacogenomics,2003,3:261-277.
2.	Hutcheson KA, Paluru PC, Bernstein SL, et al. Norrie disease gene sequence variants in an ethnically diverse population with retinopathy of prematurity[J]. Mol Vis,2005,11:501-508.
3.	Ells A, Guernsey DL, Wallace K, et al. Severe retinopathy of prematurity associated with FZD4 mutations[J]. Ophthalmic Genet,2010,31:37-43.
4.	Kondo H, Kusaka S, Yoshinaga A, et al. Genetic variants of FZD4 and LRP5 genes in patients with advanced retinopathy of prematurity[J]. Mol Vis,2013,19:476-485.
5.	Lang DM, Blackledge J, Arnold RW. Is Pacific race a retinopathy of prematurity risk factor?[J]. Arch Pediatr Adolesc Med,2005,159:771-773.
6.	Bizzarro MJ, Hussain N, Jonsson B, et al. Genetic susceptibility to retinopathy of prematurity[J]. Pediatrics,2006,118:1858-1863.
7.	Shastry BS, Pendergast SD, Hartzer MK, et al. Identification of missense mutations in the Norrie disease gene associated with advanced retinopathy of prematurity[J]. Arch Ophthalmol,1997,115:651-655.
8.	Hiraoka M, Berinstein DM, Trese MT, et al. Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity[J]. J Hum Genet,2001,46:178-181.
9.	Dickinson JL, Sale MM, Passmore A, et al. Mutations in the NDP gene:contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity[J]. Clin Exp Ophthalmol,2006,34:682-688.
10.	Hiraoka M, Takahashi H, Orimo H, et al. Genetic screening of Wnt signaling factors in advanced retinopathy of prematurity[J]. Mol Vis,2010,16:2572-2577.
11.	Awata T, Inoue K, Kurihara S, et al. A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes[J]. Diabetes,2002,51:1635-1639.
12.	Stevens A, Soden J, Brenchley PE, et al. Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter[J]. Cancer Res,2003,63:812-816.
13.	Cooke RW, Drury JA, Mountford R, et al. Genetic polymorphisms and retinopathy of prematurity[J]. Invest Ophthalmol Vis Sci,2004,45:1712-1715.
14.	Vannay A, Dunai G, Bányász I, et al. Association of genetic polymorphisms of vascular endothelial growth factor and risk for proliferative retinopathy of prematurity[J]. Pediatr Res,2005,57:396-398.
15.	Shastry BS, Qu X. Lack of association of the VEGF gene promoter (-634 G-->C and -460 C-->T) polymorphism and the risk of advanced retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol,2007,245:741-743.
16.	Kaya M, Çokakli M, Berk AT, et al. Associations of VEGF/VEGF-receptor and HGF/c-Met promoter polymorphisms with progression/regression of retinopathy of prematurity[J]. Curr Eye Res,2013,38:137-142.
17.	Liu P, Wu D, Zhou W, et al. Association of VEGF gene polymorphisms with advanced retinopathy of prematurity:a meta-analysis[J]. Mol Biol Rep,2012,39:10731-10737.
18.	Hellström A, Carlsson B, Niklasson A, et al. IGF-Ⅰ is critical for normal vascularization of the human retina[J]. J Clin Endocrinol Metab,2002,87:3413-3416.
19.	Hellström A, Perruzzi C, Ju M, et al. Low IGF-Ⅰ suppresses VEGF-survival signaling in retinal endothelial cells:direct correlation with clinical retinopathy of prematurity[J]. Proc Natl Acad Sci U S A,2001,98:5804-5808.
20.	Bonafè M, Barbieri M, Marchegiani F, et al. Polymorphic variants of insulin-like growth factor 1(IGF-1) receptor and phosphoinositide 3-kinase genes affect IGF-1 plasma levels and human longevity:cues for an evolutionarily conserved mechanism of life span control[J]. J Clin Endocrinol Metab,2003,88:3299-3304.
21.	The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity[J]. Arch Ophthalmol,1984,102:1130-1134.
22.	International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited[J]. Arch Ophthalmol,2005,123:991-999.
23.	Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity[J]. N Engl J Med,2012,367:2515-2526.
24.	Gilbert C. Retinopathy of prematurity:a global perspective of the epidemics, population of babies at risk and implications for control[J]. Early Hum Dev,2008,84:77-82.
25.	Ranchod TM, Ho LY, Drenser KA, et al. Clinical presentation of familial exudative vitreoretinopathy[J]. Ophthalmology,2011,118:2070-2075.
26.	Warden SM, Andreoli CM, Mukai S. The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease[J]. Semin Ophthalmol,2007,22:211-217.
27.	Shastry BS. SNPs:impact on gene function and phenotype[J]. Methods Mol Biol,2009,578:3-22.
28.	Poulter JA, Ali M, Gilmour DF, et al. Mutations in TSPAN12 cause autosomal-dominant familial exudative vitreoretinopathy[J]. Am J Hum Genet,2010,86:248-253.
29.	Junge HJ, Yang S, Burton JB, et al. TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/β-catenin signaling[J]. Cell,2009,139:299-311.
30.	Shastry BS. Genetic susceptibility to advanced retinopathy of prematurity (ROP)[J]. J Biomed Sci,2010,17:69.
31.	Ye X, Wang Y, Cahill H, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization[J]. Cell,2009,139:285-298.
32.	Lad EM, Cheshier SH, Kalani MY. Wnt-signaling in retinal development and disease[J]. Stem Cells Dev,2009,18:7-16.
33.	Smith LE. Pathogenesis of retinopathy of prematurity[J]. Acta Paediatr Suppl,2002,91:26-28.
34.	Shastry BS. Assessment of the contribution of insulin-like growth factor Ⅰ receptor 3174 G-->A polymorphism to the progression of advanced retinopathy of prematurity[J]. Eur J Ophthalmol,2007,17:950-953.
35.	Balogh A, Derzbach L, Vannay A, et al. Lack of association between insulin-like growth factor Ⅰ receptor G(+3174)A polymorphism and retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol,2006,244:1035-1038.
36.	Kimura H, Esumi H. Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis[J]. Acta Biochim Pol,2003,50:49-59.
37.	Yanamandra K, Napper D, Pramanik A, et al. Endothelial nitric oxide synthase genotypes in the etiology of retinopathy of prematurity in premature infants[J]. Ophthalmic Genet,2010,31:173-177.
38.	Shastry BS. Endothelial nitric oxide synthase gene promoter polymorphism (T-786C) may be associated with advanced retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol,2013,251:2251-2253.
39.	Wilkinson-Berka JL, Rana I, Armani R, et al. Reactive oxygen species, Nox and angiotensin Ⅱ in angiogenesis:implications for retinopathy[J]. Clin Sci (Lond),2013,124:597-615.
40.	Haider MZ, Devarajan LV, Al-Essa M, et al. Angiotensin-converting enzyme gene insertion/deletion polymorphism in Kuwaiti children with retinopathy of prematurity[J]. Biol Neonate,2002,82:84-88.
41.	Spiegler J, Gilhaus A, Konig IR, et al. Polymorphisms in the renin-angiotensin system and outcome of very-low-birth weight infants[J]. Neonatology,2010,97:10-14.
42.	John Baier R, Loggins J, Yanamandra K. Angiotensin converting enzyme insertion/deletion polymorphism does not alter sepsis outcome in ventilated very low birth weight infants[J]. J Perinatol,2005,25:205-209.
43.	Sood BG, Madan A, Saha S, et al. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity[J]. Pediatr Res,2010,67:394-400.
44.	Silveira RC, Fortes Filho JB, Procianoy RS. Assessment of the contribution of cytokine plasma levels to detect retinopathy of prematurity in very low birth weight infants[J]. Invest Ophthalmol Vis Sci,2011,52:1297-1301.
45.	Mohamed S, Schaa K, Cooper ME, et al. Genetic contributions to the development of retinopathy of prematurity[J]. Pediatr Res,2009,65:193-197.

1. Mechoulam H, Pierce EA. Retinopathy of prematurity:molecular pathology and therapeutic strategies[J]. Am J Pharmacogenomics,2003,3:261-277.
2. Hutcheson KA, Paluru PC, Bernstein SL, et al. Norrie disease gene sequence variants in an ethnically diverse population with retinopathy of prematurity[J]. Mol Vis,2005,11:501-508.
3. Ells A, Guernsey DL, Wallace K, et al. Severe retinopathy of prematurity associated with FZD4 mutations[J]. Ophthalmic Genet,2010,31:37-43.
4. Kondo H, Kusaka S, Yoshinaga A, et al. Genetic variants of FZD4 and LRP5 genes in patients with advanced retinopathy of prematurity[J]. Mol Vis,2013,19:476-485.
5. Lang DM, Blackledge J, Arnold RW. Is Pacific race a retinopathy of prematurity risk factor?[J]. Arch Pediatr Adolesc Med,2005,159:771-773.
6. Bizzarro MJ, Hussain N, Jonsson B, et al. Genetic susceptibility to retinopathy of prematurity[J]. Pediatrics,2006,118:1858-1863.
7. Shastry BS, Pendergast SD, Hartzer MK, et al. Identification of missense mutations in the Norrie disease gene associated with advanced retinopathy of prematurity[J]. Arch Ophthalmol,1997,115:651-655.
8. Hiraoka M, Berinstein DM, Trese MT, et al. Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity[J]. J Hum Genet,2001,46:178-181.
9. Dickinson JL, Sale MM, Passmore A, et al. Mutations in the NDP gene:contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity[J]. Clin Exp Ophthalmol,2006,34:682-688.
10. Hiraoka M, Takahashi H, Orimo H, et al. Genetic screening of Wnt signaling factors in advanced retinopathy of prematurity[J]. Mol Vis,2010,16:2572-2577.
11. Awata T, Inoue K, Kurihara S, et al. A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes[J]. Diabetes,2002,51:1635-1639.
12. Stevens A, Soden J, Brenchley PE, et al. Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter[J]. Cancer Res,2003,63:812-816.
13. Cooke RW, Drury JA, Mountford R, et al. Genetic polymorphisms and retinopathy of prematurity[J]. Invest Ophthalmol Vis Sci,2004,45:1712-1715.
14. Vannay A, Dunai G, Bányász I, et al. Association of genetic polymorphisms of vascular endothelial growth factor and risk for proliferative retinopathy of prematurity[J]. Pediatr Res,2005,57:396-398.
15. Shastry BS, Qu X. Lack of association of the VEGF gene promoter (-634 G-->C and -460 C-->T) polymorphism and the risk of advanced retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol,2007,245:741-743.
16. Kaya M, Çokakli M, Berk AT, et al. Associations of VEGF/VEGF-receptor and HGF/c-Met promoter polymorphisms with progression/regression of retinopathy of prematurity[J]. Curr Eye Res,2013,38:137-142.
17. Liu P, Wu D, Zhou W, et al. Association of VEGF gene polymorphisms with advanced retinopathy of prematurity:a meta-analysis[J]. Mol Biol Rep,2012,39:10731-10737.
18. Hellström A, Carlsson B, Niklasson A, et al. IGF-Ⅰ is critical for normal vascularization of the human retina[J]. J Clin Endocrinol Metab,2002,87:3413-3416.
19. Hellström A, Perruzzi C, Ju M, et al. Low IGF-Ⅰ suppresses VEGF-survival signaling in retinal endothelial cells:direct correlation with clinical retinopathy of prematurity[J]. Proc Natl Acad Sci U S A,2001,98:5804-5808.
20. Bonafè M, Barbieri M, Marchegiani F, et al. Polymorphic variants of insulin-like growth factor 1(IGF-1) receptor and phosphoinositide 3-kinase genes affect IGF-1 plasma levels and human longevity:cues for an evolutionarily conserved mechanism of life span control[J]. J Clin Endocrinol Metab,2003,88:3299-3304.
21. The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity[J]. Arch Ophthalmol,1984,102:1130-1134.
22. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited[J]. Arch Ophthalmol,2005,123:991-999.
23. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity[J]. N Engl J Med,2012,367:2515-2526.
24. Gilbert C. Retinopathy of prematurity:a global perspective of the epidemics, population of babies at risk and implications for control[J]. Early Hum Dev,2008,84:77-82.
25. Ranchod TM, Ho LY, Drenser KA, et al. Clinical presentation of familial exudative vitreoretinopathy[J]. Ophthalmology,2011,118:2070-2075.
26. Warden SM, Andreoli CM, Mukai S. The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease[J]. Semin Ophthalmol,2007,22:211-217.
27. Shastry BS. SNPs:impact on gene function and phenotype[J]. Methods Mol Biol,2009,578:3-22.
28. Poulter JA, Ali M, Gilmour DF, et al. Mutations in TSPAN12 cause autosomal-dominant familial exudative vitreoretinopathy[J]. Am J Hum Genet,2010,86:248-253.
29. Junge HJ, Yang S, Burton JB, et al. TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/β-catenin signaling[J]. Cell,2009,139:299-311.
30. Shastry BS. Genetic susceptibility to advanced retinopathy of prematurity (ROP)[J]. J Biomed Sci,2010,17:69.
31. Ye X, Wang Y, Cahill H, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization[J]. Cell,2009,139:285-298.
32. Lad EM, Cheshier SH, Kalani MY. Wnt-signaling in retinal development and disease[J]. Stem Cells Dev,2009,18:7-16.
33. Smith LE. Pathogenesis of retinopathy of prematurity[J]. Acta Paediatr Suppl,2002,91:26-28.
34. Shastry BS. Assessment of the contribution of insulin-like growth factor Ⅰ receptor 3174 G-->A polymorphism to the progression of advanced retinopathy of prematurity[J]. Eur J Ophthalmol,2007,17:950-953.
35. Balogh A, Derzbach L, Vannay A, et al. Lack of association between insulin-like growth factor Ⅰ receptor G(+3174)A polymorphism and retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol,2006,244:1035-1038.
36. Kimura H, Esumi H. Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis[J]. Acta Biochim Pol,2003,50:49-59.
37. Yanamandra K, Napper D, Pramanik A, et al. Endothelial nitric oxide synthase genotypes in the etiology of retinopathy of prematurity in premature infants[J]. Ophthalmic Genet,2010,31:173-177.
38. Shastry BS. Endothelial nitric oxide synthase gene promoter polymorphism (T-786C) may be associated with advanced retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol,2013,251:2251-2253.
39. Wilkinson-Berka JL, Rana I, Armani R, et al. Reactive oxygen species, Nox and angiotensin Ⅱ in angiogenesis:implications for retinopathy[J]. Clin Sci (Lond),2013,124:597-615.
40. Haider MZ, Devarajan LV, Al-Essa M, et al. Angiotensin-converting enzyme gene insertion/deletion polymorphism in Kuwaiti children with retinopathy of prematurity[J]. Biol Neonate,2002,82:84-88.
41. Spiegler J, Gilhaus A, Konig IR, et al. Polymorphisms in the renin-angiotensin system and outcome of very-low-birth weight infants[J]. Neonatology,2010,97:10-14.
42. John Baier R, Loggins J, Yanamandra K. Angiotensin converting enzyme insertion/deletion polymorphism does not alter sepsis outcome in ventilated very low birth weight infants[J]. J Perinatol,2005,25:205-209.
43. Sood BG, Madan A, Saha S, et al. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity[J]. Pediatr Res,2010,67:394-400.
44. Silveira RC, Fortes Filho JB, Procianoy RS. Assessment of the contribution of cytokine plasma levels to detect retinopathy of prematurity in very low birth weight infants[J]. Invest Ophthalmol Vis Sci,2011,52:1297-1301.
45. Mohamed S, Schaa K, Cooper ME, et al. Genetic contributions to the development of retinopathy of prematurity[J]. Pediatr Res,2009,65:193-197.

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早产儿视网膜病变遗传易感性

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