Association of Polymorphisms in the Hepatocyte Growth Factor Gene Promoter with Keratoconus

被引：96

作者：

Burdon, Kathryn P. ^{[1
]}

Macgregor, Stuart ^{[2
]}

Bykhovskaya, Yelena ^{[3
]}

Javadiyan, Sharhbanou ^{[1
]}

Li, Xiaohui ^{[3
,4
]}

Laurie, Kate J. ^{[1
]}

Muszynska, Dorota ^{[5
]}

Lindsay, Richard ^{[6
]}

Lechner, Judith ^{[5
]}

Haritunians, Talin ^{[4
]}

Henders, Anjali K. ^{[2
]}

Dash, Durga ^{[5
]}

Siscovick, David ^{[7
]}

Anand, Seema ^{[1
]}

Aldave, Anthony ^{[8
]}

Coster, Douglas J. ^{[1
]}

Szczotka-Flynn, Loretta ^{[9
]}

Mills, Richard A. ^{[1
]}

Iyengar, Sudha K. ^{[9
]}

Taylor, Kent D. ^{[4
]}

Phillips, Tony ^{[1
]}

Montgomery, Grant W. ^{[2
]}

Rotter, Jerome I. ^{[4
]}

Hewitt, Alex W. ^{[10
,11
]}

Sharma, Shiwani ^{[1
]}

Rabinowitz, Yaron S. ^{[3
]}

Willoughby, Colin ^{[5
]}

Craig, Jamie E. ^{[1
]}

机构：

[1] Flinders Univ S Australia, Flinders Med Ctr, Dept Ophthalmol, Bedford Pk, SA 5042, Australia

[2] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[3] Cedars Sinai Med Ctr, Cornea Genet Eye Inst, Los Angeles, CA 90048 USA

[4] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[5] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland

[6] Richard Lindsay & Associates, Melbourne, Vic, Australia

[7] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[8] Univ Calif Los Angeles, Jules Stein Inst, Los Angeles, CA USA

[9] Case Western Reserve Univ, Dept Ophthalmol, Cleveland, OH 44106 USA

[10] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia

[11] Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2011年 / 52卷 / 11期

基金：

英国医学研究理事会;

关键词：

AUTOSOMAL-DOMINANT KERATOCONUS; GENOME-WIDE ASSOCIATION; VSX1; GENE; INFLAMMATORY MOLECULES; FACTOR/SCATTER FACTOR; FAMILIAL KERATOCONUS; LINKAGE SCAN; LOCUS; DNA; IDENTIFICATION;

D O I：

10.1167/iovs.11-8261

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

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

引用

页码：8514 / 8519

页数：6

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