期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 53, 期 7, 页码 4152-4157出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.11-9268
关键词
-
资金
- National Institutes of Health (NIH)/National Eye Institute [NEI EY-09052]
- Skirball Foundation for Molecular Ophthalmology
- Eye Defects Research Foundation Inc.
- National Center for Research Resources (NCRR) [M01-RR-00425]
- Southern California Diabetes Endocrinology Research Center [DK063491]
- NIH NCRR Clinical and Translational Science Institute [UL1-RR-033176]
- CHS Research Contracts [N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]
- National Heart, Lung, and Blood Institute [HL-080295]
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]
PURPOSE. Keratoconus is a bilateral noninflammatory progressive corneal disorder with complex genetic inheritance and a common cause for cornea transplantation in young adults. A genomewide linkage scan in keratoconus families identified a locus at 5q23.2, overlapping the gene coding for the lysyl oxidase (LOX). LOX encodes an enzyme responsible for collagen cross-linking in a variety of tissues including the cornea. Corneal collagen cross-linking with long-wave ultraviolet light and riboflavin is a promising new treatment for keratoconus. To determine whether LOX is a genetic determinant of the pathogenesis of keratoconus, we analyzed association results of LOX polymorphisms in two independent case-control samples and in keratoconus families. METHODS. Association results were analyzed of single-nucleotide polymorphisms (SNPs) in the LOX gene from a Genome-Wide Association Study (GWAS) investigation in two independent panels of patients with keratoconus and controls and in keratoconus families. RESULTS. Evidence of association was found at SNPs rs10519694 and rs2956540 located in intron 4 of LOX in the GWAS discovery case-control panel with P values of 2.3 x 10(-3) and 7 x 10(-3), respectively. The same two SNPs were found to be associated with keratoconus by family-based association testing with P values of 2.7 x 10(-3) and 7.7 x 10(-4), respectively. Meta P values of 4.0 x 10(-5) and 4.0 x 10(-7) were calculated for SNPs rs10519694 and rs2956540 by analyzing case-control and family samples simultaneously. Sequencing of LOX exons in a subset of keratoconus patients identified two polymorphisms, rs1800449 and rs2288393, located in LOX transcripts I and II, associated with keratoconus in case-control and family samples with a meta P value of 0.02. CONCLUSIONS. Results provided strong genetic evidence that LOX variants lead to increased susceptibility to developing of keratoconus. (Invest Ophthalmol Vis Sci. 2012;53:4152-4157) DOI:10.1167/iovs.11-9268
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据