PMID- 25537207
OWN - NLM
STAT- MEDLINE
DCOM- 20150303
LR  - 20240104
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 56
IP  - 1
DP  - 2014 Dec 23
TI  - Association of common SIX6 polymorphisms with peripapillary retinal nerve fiber 
      layer thickness: the Singapore Chinese Eye Study.
PG  - 478-83
LID - 10.1167/iovs.14-15863 [doi]
AB  - PURPOSE: Recently the common SIX6 missense variant rs33912345 was found to be 
      highly associated with glaucoma. The aim of this study was to investigate the 
      association between this SIX6 variant and peripapillary retinal nerve fiber layer 
      (RNFL) thickness measured by spectral-domain optical coherence tomography 
      (SD-OCT) in a population setting. METHODS: Study subjects were enrolled from the 
      Singapore Chinese Eye Study (SCES), a population-based survey of Singaporean 
      Chinese aged 40 years or older. Subjects underwent a comprehensive ocular 
      examination. Spectral-domain OCT was used to measure RNFL thicknesses. Genotyping 
      of SIX6 rs33912345 (Asn141His) was performed using HumanExome BeadChip. RESULTS: 
      A total of 2129 eyes from 1243 SCES subjects (mean age: 55.0 +/- 7.4 years) with 
      rs33912345 genotype data and SD-OCT images were included for the analysis. Of 
      these, 26 eyes of 21 subjects had glaucoma. The frequency of rs33912345 risk 
      variant C (His141) was 80% in the study subjects. Each rs33912345 C allele was 
      associated with a decrease of 1.44 mum in RNFL thickness after adjusting for age, 
      sex, genetic principal components, and axial length (P = 0.001). These 
      associations remained similar in 2096 nonglaucoma eyes in which each C allele was 
      associated with a decrease of 1.39 mum in RNFL thickness (P = 0.001). The 
      strongest association was observed in the superior RNFL sector (a decrease of 
      2.83 mum per risk allele, P < 0.001) followed by the inferior RNFL sector (a 
      decrease of 2.24 mum per risk allele, P = 0.003), while the association did not 
      reach significance in the nasal and temporal sectors. CONCLUSIONS: 
      Nonglaucomatous individuals with the SIX6 missense variant have reduced RNFL 
      thickness in regions known to be particularly affected in those with glaucoma. 
      This may be the primary mechanism for increased risk of POAG in individuals who 
      carry the SIX6 His141 risk variant.
CI  - Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
FAU - Cheng, Ching-Yu
AU  - Cheng CY
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
FAU - Allingham, R Rand
AU  - Allingham RR
AD  - Department of Ophthalmology, Duke University Medical Center, Durham, North 
      Carolina, United States.
FAU - Aung, Tin
AU  - Aung T
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 
      Department of Ophthalmology, Yong Loo Lin School of Medicine, National University 
      of Singapore and National University Health System, Singapore.
FAU - Tham, Yih-Chung
AU  - Tham YC
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 
      Department of Ophthalmology, Yong Loo Lin School of Medicine, National University 
      of Singapore and National University Health System, Singapore.
FAU - Hauser, Michael A
AU  - Hauser MA
AD  - Department of Ophthalmology, Duke University Medical Center, Durham, North 
      Carolina, United States.
FAU - Vithana, Eranga N
AU  - Vithana EN
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 
      Duke-NUS Graduate Medical School, Singapore.
FAU - Khor, Chiea Chuen
AU  - Khor CC
AD  - Division of Human Genetics, Genome Institute of Singapore, Singapore.
FAU - Wong, Tien Yin
AU  - Wong TY
AD  - Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
LA  - eng
GR  - P30 EY005722/EY/NEI NIH HHS/United States
GR  - R01 EY023646/EY/NEI NIH HHS/United States
GR  - 5P30-EY005722/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141223
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Eye Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (SIX6 protein, human)
RN  - 0 (Trans-Activators)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cross-Sectional Studies
MH  - DNA/*genetics
MH  - Eye Proteins
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - Glaucoma, Open-Angle/epidemiology/*genetics/metabolism
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nerve Fibers/metabolism/*pathology
MH  - *Polymorphism, Genetic
MH  - Retinal Ganglion Cells/metabolism/*pathology
MH  - Retrospective Studies
MH  - Singapore/epidemiology
MH  - Tomography, Optical Coherence/methods
MH  - Trans-Activators/*genetics/metabolism
PMC - PMC4544593
OTO - NOTNLM
OT  - SIX6
OT  - genetic association
OT  - glaucoma
OT  - retinal nerve fiver layer thickness
EDAT- 2014/12/30 06:00
MHDA- 2015/03/04 06:00
PMCR- 2015/07/01
CRDT- 2014/12/25 06:00
PHST- 2014/12/25 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/03/04 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - iovs.14-15863 [pii]
AID - 10.1167/iovs.14-15863 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 Dec 23;56(1):478-83. doi: 10.1167/iovs.14-15863.