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Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus.
Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
| Title | Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Burdon, KP, Macgregor, S, Bykhovskaya, Y, Javadiyan, S, Li, X, Laurie, KJ, Muszynska, D, Lindsay, R, Lechner, J, Haritunians, T, Henders, AK, Dash, D, Siscovick, D, Anand, S, Aldave, A, Coster, DJ, Szczotka-Flynn, L, Mills, RA, Iyengar, SK, Taylor, KD, Phillips, T, Montgomery, GW, Rotter, JI, Hewitt, AW, Sharma, S, Rabinowitz, YS, Willoughby, C, Craig, JE |
| Journal | Invest Ophthalmol Vis Sci |
| Volume | 52 |
| Issue | 11 |
| Pagination | 8514-9 |
| Date Published | 2011 Oct 31 |
| ISSN | 1552-5783 |
| Keywords | Adult, Aged, Chromosomes, Human, Pair 7, Corneal Topography, Enzyme-Linked Immunosorbent Assay, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Hepatocyte Growth Factor, Humans, Keratoconus, Middle Aged, Nucleic Acid Hybridization, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Sequence Tagged Sites |
| Abstract | <p><b>PURPOSE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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 = 9.9 × 10(-7)) and rs17501108 (P = 9.9 × 10(-5)). In addition, SNP rs3735520 was found to be associated with serum HGF level in normal individuals (P = 0.036).</p><p><b>CONCLUSIONS: </b>Taken together, these results implicate genetic variation at the HGF locus with keratoconus susceptibility.</p> |
| DOI | 10.1167/iovs.11-8261 |
| Alternate Journal | Invest. Ophthalmol. Vis. Sci. |
| PubMed ID | 22003120 |
| PubMed Central ID | PMC3208191 |
| Grant List | M01-RR00425 / RR / NCRR NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI 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 N01-HC-85082 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States NEI-09052 / / PHS HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States |