- 作者：Stephanie J. Loomis ; Jae H. Kang ; Robert N. Weinreb ; Brian L. Yaspan ; Jessica N. Cooke Bailey ; Douglas Gaasterl ; Terry Gaasterl ; Richard K. Lee ; Paul R. Lichter ; Donald L. Budenz ; Yutao Liu ; Tony Realini ; David S. Friedman ; Catherine A. McCarty ; Sayoko E. Moroi ; Lana Olson ; Joel S. Schuman ; Kuldev Singh ; Douglas Vollrath ; Gadi Wollstein ; Donald J. Zack ; et al.
- 刊名：Ophthalmology
- 出版年：February, 2014
- 年：2014
- 卷：121
- 期：2
- 页码：508-516
- 全文大小：740 K
Purpose
The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further.Design
Case-control study.
Participants
We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls).
Methods
We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7脳10鈭? was used to account for multiple comparisons.
Main Outcome Measures
Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss.
Results
We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P聽= 2.61脳10鈭?). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P聽= 1.59脳10鈭?). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P聽= 1.07脳10鈭?), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men.
Conclusions
CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.