PURPOSE: Genome-wide association studies have shown association of the atonal homolog 7 (ATOH7) and raftlin lipid raft linker 1 (RFTN1) genes with glaucoma-related optic disc parameters. ATOH7 and RFTN1 sequence variations were investigated in patients with primary open-angle glaucoma (POAG) and their relationships with vertical cup-to-disc ratio (VCDR) and central corneal thickness (CCT) were determined. METHODS: In 289 unrelated controls and 142 patients with adult-onset POAG, including 117 with high-tension glaucoma (HTG) and 25 with normal-tension glaucoma (NTG), the single exon of ATOH7 was sequenced by direct sequencing. Additional single-nucleotide polymorphisms (SNP) at upstream ATOH7 (rs1900004 and rs3858145) and an RFTN1 SNP (rs690037) were genotyped. Quantitative trait and disease associations were analyzed by linear and logistic regression respectively, controlling for sex and age. RESULTS: ATOH7 rs61854782 was associated with VCDR (P = 0.004) in controls and RFTN1 rs690037 was associated with CCT in combined POAG (HTG+NTG; P = 0.026). No coding mutation was detected in POAG, and no SNP was associated with POAG (P between 0.441 and 0.996). However, ATOH7 rs3858145 showed significant interaction with RFTN1 rs690037 in NTG and combined POAG (P = 0.026 and 0.013 respectively). ATOH7 rs3858145 GG combined with RFTN1 rs690037 TT conferred risk for glaucoma in HTG, NTG, and combined POAG (odds ratio = 2.11, 8.44, and 2.69, respectively). CONCLUSIONS: Coding mutations of ATOH7 were unlikely to be involved in POAG. But combination of ATOH7 and RFTN1 SNPs increased risk to POAG, indicating their diversified effects in the complex genetics of glaucoma.
PURPOSE: Genome-wide association studies have shown association of the atonal homolog 7 (ATOH7) and raftlin lipid raft linker 1 (RFTN1) genes with glaucoma-related optic disc parameters. ATOH7 and RFTN1 sequence variations were investigated in patients with primary open-angle glaucoma (POAG) and their relationships with vertical cup-to-disc ratio (VCDR) and central corneal thickness (CCT) were determined. METHODS: In 289 unrelated controls and 142 patients with adult-onset POAG, including 117 with high-tension glaucoma (HTG) and 25 with normal-tension glaucoma (NTG), the single exon of ATOH7 was sequenced by direct sequencing. Additional single-nucleotide polymorphisms (SNP) at upstream ATOH7 (rs1900004 and rs3858145) and an RFTN1 SNP (rs690037) were genotyped. Quantitative trait and disease associations were analyzed by linear and logistic regression respectively, controlling for sex and age. RESULTS:ATOH7rs61854782 was associated with VCDR (P = 0.004) in controls and RFTN1rs690037 was associated with CCT in combined POAG (HTG+NTG; P = 0.026). No coding mutation was detected in POAG, and no SNP was associated with POAG (P between 0.441 and 0.996). However, ATOH7rs3858145 showed significant interaction with RFTN1rs690037 in NTG and combined POAG (P = 0.026 and 0.013 respectively). ATOH7rs3858145 GG combined with RFTN1rs690037 TT conferred risk for glaucoma in HTG, NTG, and combined POAG (odds ratio = 2.11, 8.44, and 2.69, respectively). CONCLUSIONS: Coding mutations of ATOH7 were unlikely to be involved in POAG. But combination of ATOH7 and RFTN1 SNPs increased risk to POAG, indicating their diversified effects in the complex genetics of glaucoma.
Authors: Lev Prasov; Tehmina Masud; Shagufta Khaliq; S Qasim Mehdi; Aiysha Abid; Edward R Oliver; Eduardo D Silva; Amy Lewanda; Michael C Brodsky; Mark Borchert; Daniel Kelberman; Jane C Sowden; Mehul T Dattani; Tom Glaser Journal: Hum Mol Genet Date: 2012-05-29 Impact factor: 6.150
Authors: Yutao Liu; Melanie E Garrett; Brian L Yaspan; Jessica Cooke Bailey; Stephanie J Loomis; Murray Brilliant; Donald L Budenz; William G Christen; John H Fingert; Douglas Gaasterland; Terry Gaasterland; Jae H Kang; Richard K Lee; Paul Lichter; Sayoko E Moroi; Anthony Realini; Julia E Richards; Joel S Schuman; William K Scott; Kuldev Singh; Arthur J Sit; Douglas Vollrath; Robert Weinreb; Gadi Wollstein; Donald J Zack; Kang Zhang; Margaret A Pericak-Vance; Jonathan L Haines; Louis R Pasquale; Janey L Wiggs; R Rand Allingham; Allison E Ashley-Koch; Michael A Hauser Journal: Invest Ophthalmol Vis Sci Date: 2014-11-20 Impact factor: 4.799
Authors: Jessica N Cooke Bailey; Stephanie J Loomis; Jae H Kang; R Rand Allingham; Puya Gharahkhani; Chiea Chuen Khor; Kathryn P Burdon; Hugues Aschard; Daniel I Chasman; Robert P Igo; Pirro G Hysi; Craig A Glastonbury; Allison Ashley-Koch; Murray Brilliant; Andrew A Brown; Donald L Budenz; Alfonso Buil; Ching-Yu Cheng; Hyon Choi; William G Christen; Gary Curhan; Immaculata De Vivo; John H Fingert; Paul J Foster; Charles Fuchs; Douglas Gaasterland; Terry Gaasterland; Alex W Hewitt; Frank Hu; David J Hunter; Anthony P Khawaja; Richard K Lee; Zheng Li; Paul R Lichter; David A Mackey; Peter McGuffin; Paul Mitchell; Sayoko E Moroi; Shamira A Perera; Keating W Pepper; Qibin Qi; Tony Realini; Julia E Richards; Paul M Ridker; Eric Rimm; Robert Ritch; Marylyn Ritchie; Joel S Schuman; William K Scott; Kuldev Singh; Arthur J Sit; Yeunjoo E Song; Rulla M Tamimi; Fotis Topouzis; Ananth C Viswanathan; Shefali Setia Verma; Douglas Vollrath; Jie Jin Wang; Nicole Weisschuh; Bernd Wissinger; Gadi Wollstein; Tien Y Wong; Brian L Yaspan; Donald J Zack; Kang Zhang; Epic-Norfolk Eye Study; Robert N Weinreb; Margaret A Pericak-Vance; Kerrin Small; Christopher J Hammond; Tin Aung; Yutao Liu; Eranga N Vithana; Stuart MacGregor; Jamie E Craig; Peter Kraft; Gareth Howell; Michael A Hauser; Louis R Pasquale; Jonathan L Haines; Janey L Wiggs Journal: Nat Genet Date: 2016-01-11 Impact factor: 38.330