eCite Digital Repository

Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus


Burdon, KP and Macgregor, S and Bykhovskaya, Y and Javadiyan, S and Li, X and Laurie, KJ and Muszynska, D and Lindsay, R and Lechner, J and Haritunians, T and Henders, AK and Dash, D and Siscovick, D and Anand, S and Aldave, A and Coster, DJ and Szczotka-Flynn, L and Mills, RA and Iyengar, SK and Taylor, KD and Phillips, T and Montgomery, GW and Rotter, JI and Hewitt, AW and Sharma, S and Rabinowitz, YS and Willoughby, C and Craig, JE, Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus, Investigative Ophthalmology and Visual Science, 52, (11) pp. 8514-8519. ISSN 0146-0404 (2011) [Refereed Article]

Restricted - Request a copy

Copyright Statement

Copyright 2011 The Association for Research in Vision and Opthaltmology Inc.

Official URL:

DOI: doi:10.1167/iovs.11-8261


Purpose: Keratoconus is a progressive disorder of the cornea that can lead to severe visual impairment or blindness. Although several genomic regions have been linked to rare familial forms of keratoconus, no genes have yet been definitively identified for common forms of the disease.

Methods: Two genome-wide association scans were undertaken in parallel. The first used pooled DNA from an Australian cohort, followed by typing of top-ranked single-nucleotide polymorphisms (SNPs) in individual DNA samples. The second was conducted in individually genotyped patients, and controls from the USA. Tag SNPs around the hepatocyte growth factor (HGF) gene were typed in three additional replication cohorts. Serum levels of HGF protein in normal individuals were assessed with ELISA and correlated with genotype.

Results: The only SNP observed to be associated in both the pooled discovery and primary replication cohort was rs1014091, located upstream of the HGF gene. The nearby SNP rs3735520 was found to be associated in the individually typed discovery cohort (P = 6.1 10-7). Genotyping of tag SNPs around HGF revealed association at rs3735520 and rs17501108/rs1014091 in four of the five cohorts. Meta-analysis of all five datasets together yielded suggestive P values for rs3735520 (P= 9.9נ10-7) and rs17501108 (P=9.9נ10-5). In addition, SNP rs3735520 was found to be associated with serum HGF level in normal individuals (P=0.036).

Conclusions: Taken together, these results implicate genetic variation at the HGF locus with keratoconus susceptibility.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:90670
Year Published:2011
Web of Science® Times Cited:86
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-04-16
Last Modified:2017-11-06

Repository Staff Only: item control page