Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.
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.
Department of Ophthalmology & Vision Science, Eye & Ear Nose Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
Xueli
X
Chen
Department of Ophthalmology & Vision Science, Eye & Ear Nose Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yuhong
Y
Chen
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
Janey L
JL
Wiggs
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Louis R
LR
Pasquale
Department of Ophthalmology & Vision Science, Eye & Ear Nose Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.|State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.|Key Laboratory of Myopia, Ministry of Health (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, China.
Xinghuai
X
Sun
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
Bao Jian
BJ
Fan
D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015812:Glaucoma, Angle-Closure / Q000235:genetics*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9