You are here
Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies.
Monday,2013-01-14 16:53 America/Los_Angeles — poolea2
| Title | Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Bykhovskaya, Y, Li, X, Epifantseva, I, Haritunians, T, Siscovick, D, Aldave, A, Szczotka-Flynn, L, Iyengar, SK, Taylor, KD, Rotter, JI, Rabinowitz, YS |
| Journal | Invest Ophthalmol Vis Sci |
| Volume | 53 |
| Issue | 7 |
| Pagination | 4152-7 |
| Date Published | 2012 Jun 28 |
| ISSN | 1552-5783 |
| Keywords | Case-Control Studies, Cornea, Corneal Topography, DNA, Family, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Keratoconus, Polymorphism, Genetic, Protein-Lysine 6-Oxidase |
| Abstract | <p><b>PURPOSE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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 2.3×10(-3) and 7×10(-3), respectively. The same two SNPs were found to be associated with keratoconus by family-based association testing with P values of 2.7×10(-3) and 7.7×10(-4), respectively. Meta P values of 4.0×10(-5) and 4.0×10(-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.</p><p><b>CONCLUSIONS: </b>Results provided strong genetic evidence that LOX variants lead to increased susceptibility to developing of keratoconus.</p> |
| DOI | 10.1167/iovs.11-9268 |
| Alternate Journal | Invest. Ophthalmol. Vis. Sci. |
| PubMed ID | 22661479 |
| PubMed Central ID | PMC3760233 |
| Grant List | UL1 RR033176 / RR / NCRR NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States EY-09052 / EY / NEI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States M01-RR-00425 / RR / NCRR NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01 EY009052 / EY / NEI NIH HHS / United States HL-080295 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States UL1-RR-033176 / RR / NCRR NIH HHS / United States |