MMP9和MMP20基因多态性与老年性黄斑变性风险的相关性分析
摘要
目的研究基质金属蛋白酶9(MMP9)和MMP20基因多态性与老年性黄斑变性(AMD)风险的相关性。方法选择2015年9月-2017年9月内江市第一人民医院眼科收治的AMD患者和体检健康人群各150例,收集血样。采用Sequenom MassARRAY SNP基因分型技术对MMP9和MMP20基因上rs17576、rs3787268、rs2274755和rs10895322四个SNP进行分型。结果 AMD组和对照组间性别、年龄、BMI、糖尿病、血脂异常、甲状腺功能异常及吸烟情况的差异均无统计学意义(P>0.05)。四个SNP均符合Hardy-Weinberg平衡定律(P-HWE>0.05)。AMD组中rs17576、rs3787268和rs2274755的最小等位基因频率均显著高于对照组;而rs10895322的最小等位基因频率显著低于对照组(P <0. 05)。AMD组rs17576位点的AG和GG基因型频率、rs3787268位点的GA和AA基因型频率、rs2274755位点的GT和TT基因型频率均显著高于对照组;而rs10895322位点的AG和GG基因型频率显著低于对照组(P<0.05)。此外,rs17576和rs2274755在三个遗传模型下均与增高AMD风险具有相关性; rs3787268位点在隐性和加性模型下与增高AMD风险具有相关性;而rs10895322位点在隐性和加性模型下与降低AMD风险具有相关性(P<0.05)。结论 MMP9基因上rs17576、rs3787268和rs2274755位点可能与增加AMD风险相关,而MMP20基因上rs10895322位点可能与降低AMD风险相关。
引文
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[2]FIOTTI N,PEDIO M,BATTAGLIA P M,et al.MMP-9microsatellite polymorphism and susceptibility to exudative form of age-related macular degeneration[J].Genet Med,2005,7(4):272.
[3]DEANGELIS M M,SILVEIRA A C,CARR E A,et al.Genetics of age-related macular degeneration:current concepts,future directions[J].Semin Ophthalmol,2011,26(3):77.
[4]ZENG R,ZHANG X,WU K,et al.MMP9 gene polymorphism is not associated with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a chinese han population[J].Ophthalmic Paed Genet,2014,35(4):235.
[5]AKAGI-KURASHIGE Y,YAMASHIRO K,GOTOH N,et al.MMP20 and ARMS2/HTRA1 are associated with neovascular lesion size in age-related macular degeneration[J].Ophthalmology,2015,122(11):2295.
[6]AUTHORS U.Evaluation of the clinical age-related maculopathy staging system[J].Ophthalmology,2006,113(2):260.
[7]KLEIN R J,ZEISS C,CHEW E Y,et al.Complement factor H polymorphism in age-related macular degeneration[J].Science,2005,308(5720):385.
[8]COOKE BAILEY J N,SOBRIN L,PERICAK-VANCE MA,et al.Advances in the genomics of common eye diseases[J].Hum Mol Genet,2013,22(1):R59.
[9]CHONG N H,KEONIN J,LUTHERT P J,et al.Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration[J].Am J Ophthalmol,2005,139(6):1151.
[10]NAKASHIZUKA H,MITSUMATA M,OKISAKA S,et al.Clinicopathologic findings in polypoidal choroidal vasculopathy[J].Invest Ophthalmol Vis Sci,2008,49(11):4729.
[11]GROSSNIKLAUS H E,MISKALA P H,GREEN W R,et al.Histopathologic and ultrastructural features of surgically excised subfoveal choroidal neovascular lesions:submacular surgery trials report no.7[J].Arch Ophthalmol,2005,123(7):914.
[12]JOACHIM N D,MITCHELL P,KIFLEY A,et al.Incidence,progression,and associated risk factors of medium drusen in age-related macular degeneration:findings from the 15-year follow-up of an australian cohort[J].JAMA Ophthalmol,2015,133(6):698.
[13]GRANT G M,GIAMBERNARDI T A,GRANT A M,et al.Overview of expression of matrix metalloproteinases(MMP-17,MMP-18,and MMP-20)in cultured human cells[J].Matrix Biol,1999,18(2):145.
[14]KALAYOGLU M V,BULA D,ARROYO J,et al.Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration[J].Graef Arch Clin Exp Ophthalmol,2005,243(11):1080.
[15]WOLFSCHNURRBUSCH U E,HESS R,JORDI F,et al.Detection of Chlamydia and complement factors in neovascular membranes of patients with age-related macular degeneration[J].Ocul Immunol Inflamm,2013,21(1):36.