OBJECTIVE: Refractive errors such as myopia and hypermetropia are among the leading causes of visual impairment worldwide. Several genetic loci have been associated with myopia but none to date have been reported for hypermetropia. We investigated the hepatocyte growth factor (HGF) as a candidate gene influencing these 2 refractive error states. DESIGN: Case-control study. PARTICIPANTS: A total of 551 individuals (193 males, 358 females; mean age, 55.41+/-12.65 years) including 117 individuals with high myopia <or= -6.00 diopters (D), 140 individuals with low/moderate myopia (-2.00 to -5.99 D), 148 emmetropic individuals (-0.50 to +0.75 D) and 146 hyperopic individuals (>+2.00 D) were included in the analysis from 3 different Australian population cohorts (The Genes in Myopia Study, the Blue Mountains Eye Study, and the Melbourne Visual impairment project). METHODS: Genotyping of 9 tag single nucleotide polymorphisms (SNPs) that encompassed the entire HGF gene and its associated sequences as well as 6 additional SNPs identified through DNA resequencing was undertaken. MAIN OUTCOME MEASURES: Genetic association with refraction. RESULTS: After correction for multiple testing, the SNPs rs12536657 (odds ratio [OR], 5.53; 95% confidence interval [CI], 1.14-26.76) and rs5745718 (OR, 2.24; 95% CI, 1.30-3.85) showed significant association with hypermetropia. Whereas the SNPs rs1743 (OR, 2.02; 95% CI, 1.19-3.43; P = .009), rs4732402 (OR, 2.03; 95% CI, 1.23-3.36; P = 0.005), rs12536657 (OR, 2.38; 95% CI, 1.40-4.05; P = 0.001), rs10272030 (OR, 2.22; 95% CI, 1.31-3.75; P = 0.003), and rs9642131 (OR, 2.44; 95% CI, 1.43-4.14; P = 0.001) showed significant association with low/moderate myopia. CONCLUSIONS: These findings present the HGF gene as the first gene significantly associated with hypermetropia as well as providing evidence of significant association with myopia in a second ethnic population. In addition, it provides insights into the important biological mechanisms that regulate human ocular development (emmetropization), which are currently poorly understood. Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
OBJECTIVE: Refractive errors such as myopia and hypermetropia are among the leading causes of visual impairment worldwide. Several genetic loci have been associated with myopia but none to date have been reported for hypermetropia. We investigated the hepatocyte growth factor (HGF) as a candidate gene influencing these 2 refractive error states. DESIGN: Case-control study. PARTICIPANTS: A total of 551 individuals (193 males, 358 females; mean age, 55.41+/-12.65 years) including 117 individuals with high myopia <or= -6.00 diopters (D), 140 individuals with low/moderate myopia (-2.00 to -5.99 D), 148 emmetropic individuals (-0.50 to +0.75 D) and 146 hyperopic individuals (>+2.00 D) were included in the analysis from 3 different Australian population cohorts (The Genes in Myopia Study, the Blue Mountains Eye Study, and the Melbourne Visual impairment project). METHODS: Genotyping of 9 tag single nucleotide polymorphisms (SNPs) that encompassed the entire HGF gene and its associated sequences as well as 6 additional SNPs identified through DNA resequencing was undertaken. MAIN OUTCOME MEASURES: Genetic association with refraction. RESULTS: After correction for multiple testing, the SNPs rs12536657 (odds ratio [OR], 5.53; 95% confidence interval [CI], 1.14-26.76) and rs5745718 (OR, 2.24; 95% CI, 1.30-3.85) showed significant association with hypermetropia. Whereas the SNPs rs1743 (OR, 2.02; 95% CI, 1.19-3.43; P = .009), rs4732402 (OR, 2.03; 95% CI, 1.23-3.36; P = 0.005), rs12536657 (OR, 2.38; 95% CI, 1.40-4.05; P = 0.001), rs10272030 (OR, 2.22; 95% CI, 1.31-3.75; P = 0.003), and rs9642131 (OR, 2.44; 95% CI, 1.43-4.14; P = 0.001) showed significant association with low/moderate myopia. CONCLUSIONS: These findings present the HGF gene as the first gene significantly associated with hypermetropia as well as providing evidence of significant association with myopia in a second ethnic population. In addition, it provides insights into the important biological mechanisms that regulate human ocular development (emmetropization), which are currently poorly understood. Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Authors: Kathryn P Burdon; Stuart Macgregor; Yelena Bykhovskaya; Sharhbanou Javadiyan; Xiaohui Li; Kate J Laurie; Dorota Muszynska; Richard Lindsay; Judith Lechner; Talin Haritunians; Anjali K Henders; Durga Dash; David Siscovick; Seema Anand; Anthony Aldave; Douglas J Coster; Loretta Szczotka-Flynn; Richard A Mills; Sudha K Iyengar; Kent D Taylor; Tony Phillips; Grant W Montgomery; Jerome I Rotter; Alex W Hewitt; Shiwani Sharma; Yaron S Rabinowitz; Colin Willoughby; Jamie E Craig Journal: Invest Ophthalmol Vis Sci Date: 2011-10-31 Impact factor: 4.799
Authors: Milly S Tedja; Annechien E G Haarman; Magda A Meester-Smoor; Jaakko Kaprio; David A Mackey; Jeremy A Guggenheim; Christopher J Hammond; Virginie J M Verhoeven; Caroline C W Klaver Journal: Invest Ophthalmol Vis Sci Date: 2019-02-28 Impact factor: 4.799
Authors: Dwight Stambolian; Robert Wojciechowski; Konrad Oexle; Mario Pirastu; Xiaohui Li; Leslie J Raffel; Mary Frances Cotch; Emily Y Chew; Barbara Klein; Ronald Klein; Tien Y Wong; Claire L Simpson; Caroline C W Klaver; Cornelia M van Duijn; Virginie J M Verhoeven; Paul N Baird; Veronique Vitart; Andrew D Paterson; Paul Mitchell; Seang Mei Saw; Maurizio Fossarello; Krista Kazmierkiewicz; Federico Murgia; Laura Portas; Maria Schache; Andrea Richardson; Jing Xie; Jie Jin Wang; Elena Rochtchina; Ananth C Viswanathan; Caroline Hayward; Alan F Wright; Ozren Polasek; Harry Campbell; Igor Rudan; Ben A Oostra; André G Uitterlinden; Albert Hofman; Fernando Rivadeneira; Najaf Amin; Lennart C Karssen; Johannes R Vingerling; S M Hosseini; Angela Döring; Thomas Bettecken; Zoran Vatavuk; Christian Gieger; H-Erich Wichmann; James F Wilson; Brian Fleck; Paul J Foster; Fotis Topouzis; Peter McGuffin; Xueling Sim; Michael Inouye; Elizabeth G Holliday; John Attia; Rodney J Scott; Jerome I Rotter; Thomas Meitinger; Joan E Bailey-Wilson Journal: Hum Mol Genet Date: 2013-03-07 Impact factor: 6.150