期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 52, 期 11, 页码 8514-8519出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.11-8261
关键词
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资金
- Ramaciotti Foundation
- Ophthalmic Research Institute of Australia
- Career Development Awards
- Practitioner Fellowship
- National Health and Medical Research Council of Australia [496675]
- Fight for Sight (UK) PhD Scholarship
- Research and Development Office, Northern Ireland RRG from the National Eye Institute [4.46, NEI-09052]
- National Centre for Research Resources [M01-RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases (Southern California Diabetes Endocrinology Research Center), Bethesda, MD [DK063491]
- Eye Defects Research Foundation Inc.
- National Heart, Lung, and Blood Institute [U01 HL080295, R01 HL087652]
- National Institute of Neurologic Disorders and Stroke, Bethesda, MD
- [N01-HC-85079]
- [N01-HC-85086]
- [N01-HC-35129]
- [N01-HC-15103]
- [N01-HC-55222]
- [N01-HC-75150]
- [N01-HC-45133]
- Public Health Agency [RRG/3240/05] Funding Source: researchfish
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 x 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 = 9.9 x 10(-7)) and rs17501108 (P = 9.9 x 10(-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. (Invest Ophthalmol Vis Sci. 2011;52:8514-8519) DOI:10.1167/iovs.11-8261
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