Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-analysis

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• 作者：Shi Song Rong ; PhD¹ ; Fang Yao Tang ; MBBS¹ ; Wai Kit Chu ; DPhil¹ ; Li Ma ; MMed¹ ; Jason C.S. Yam ; FRCS (Edin)¹ ; ² ; ³ ; Shu Min Tang ; MMed¹ ; Jian Li ; MMed¹ ; Hong Gu ; PhD¹ ; Alvin L. Young ; FRCSI¹ ; ² ; Clement C. Tham ; FRCS (Glas)¹ ; ² ; ³ ; Chi Pui Pang ; DPhil¹ ; Li Jia Chen ; PhD¹ ; ² ; ^{lijia_chen@cuhk.edu.hk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AACG ; acute angle-closure glaucoma ; ACG ; angle-closure glaucoma ; CI ; confidence interval ; GWAS ; genome-wide association study ; HSP70 ; heat shock protein 70 ; HWE ; Hardy&ndash ; Weinberg equilibrium ; IOP ; intraocular pressure ; ITC ; irido-trabecular contact ; NOS ; Newcastle Ottawa Scale ; NOS3 ; nitric oxide synthase 3 ; OR ; odds ratio ; PAC ; primary angle-closure ; PACD ; primary angle-closure disease ; PACG ; primary angle-closure glaucoma ; PACS ; primary angle-closure suspect ; PAS ; peripheral anterior synec
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：123
• 期：6
• 页码：1211-1221
• 全文大小：637 K

文摘

Systematic review and meta-analysis of the genetic associations of primary angle-closure disease (PACD).

Clinical Relevance

To confirm the genetic biomarkers for PACD, including primary angle-closure glaucoma (PACG) and related phenotypes.

Methods

We searched in the MEDLINE and EMBASE databases for genetic studies of PACG or other PACD published from the start dates of the databases to May 11, 2015. We estimated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for each polymorphism in PACG, primary angle-closure suspect (PACS), and primary angle-closure (PAC) using fixed- or random-effect models. We also performed sensitivity analysis to test the robustness of the results.

Results

Our literature search yielded 6463 reports. Among them, we identified 24 studies that fulfilled the eligibility criteria for meta-analysis, involving 28 polymorphisms in 11 genes/loci. We affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci, including COL11A1 (rs3753841-G, OR, 1.22; P = 0.00046), HGF (rs17427817-C, OR, 2.02; P = 6.9E-07; rs5745718-A, OR, 2.11; P = 9.9E-07), HSP70 (rs1043618, GG+GC, OR, 0.52; P = 0.0010), MFRP (rs2510143-C, OR, 0.66; P = 0.012; rs3814762-G, OR, 1.40; P = 0.0090), MMP9 (rs3918249-C, OR, 1.35; P = 0.034), NOS3 (rs7830-A, OR, 0.80; P = 0.036), PLEKHA7 (rs11024102-G, OR, 1.24; P = 8.3E-05), and PCMTD1-ST18 (rs1015213-A, OR, 1.59; P = 0.00013). Sensitivity analysis indicated that the results were robust.

Conclusions

In this study, we confirmed multiple polymorphisms in 8 genes/loci as genetic biomarkers for PACD, among which 3 were identified in a genome-wide association study (COL11A1, PLEKHA7, and PCMTD1-ST18), and 5 were identified in candidate gene studies (HGF, HSP70, MFRP, MMP9, and NOS3).