Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.
Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.
复制标题
基质金属蛋白酶 9 (MMP9) 变异体与原发性闭角型青光眼的关联。
DOI：
10.1371/journal.pone.0157093
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Fan BJ
中科院分区：
文献类型：
--
作者：
Chen X;Chen Y;Wiggs JL;Pasquale LR;Sun X;Fan BJ
原发性闭角型青光眼（PACG）患者中观察到的较短眼轴长度可能是由于基质金属蛋白酶 - 9（MMP9）活性改变，导致眼睛生长发育过程中细胞外基质重塑。本研究旨在评估MMP9的常见变异与PACG的相关性。在中国的1030个样本中对MMP9的6个标签单核苷酸多态性（SNP）进行了基因分型，其中包括572例PACG和458例原发性房角关闭（PAC）患者以及499例对照。6个SNP与总体PAC/PACG均无显著相关性（P > 0.07），与PAC/PACG亚组也无显著相关性（校正P值 > 0.18）。对两项非中国研究的荟萃分析显示rs17576与PACG之间存在显著相关性（比值比 = 0.56，P < 0.0001）；然而，将我们的数据与4个中国数据集进行荟萃分析时，未重复出这种相关性（比值比 = 1.23，P = 0.29）。一项高加索人研究中先前发现rs3918249具有显著相关性（比值比 = 0.63，P = 0.006），但在包括本研究在内的3项中国研究的荟萃分析中未重复出该相关性（比值比 = 0.91，P = 0.13）。非中国数据集和中国数据集之间存在显著异质性，妨碍了对rs17576和rs3918249进行总体荟萃分析（分别为Q = 0.001和0.04）。rs17577在一项高加索人研究中与PACG名义上相关（比值比 = 1.71，P = 0.02），但在包括我们研究在内的3项中国研究中不相关（比值比 = 1.20，P = 0.07）。总体荟萃分析显示rs17577与PAC/PACG名义上相关（比值比 = 1.26，校正P值 = 0.05）。荟萃分析未显示其他SNP与PAC/PACG之间存在显著相关性（P > 0.47）。迄今为止最大规模的相关性研究未发现MMP9与中国人群中的PAC/PACG之间存在显著相关性；与其他中国数据集的荟萃分析也未产生显著相关性。在大多数情况下，除了一个变异显示名义上显著相关外，无法与非中国数据集合并。需要更多的工作来确定MMP9变异在PACG中的作用。
Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.