Association of genetic variants in the TMCO1 gene with clinical parameters related to glaucoma and characterization of the protein in the eye

Sharma, Shiwani, Burdon, Kathryn P., Chidlow, Glyn, Klebe, Sonja, Crawford, April, Dimasi, David P., Dave, Alpana, Martin, Sarah, Javadiyan, Shahrbanou, Wood, John P. M., Casson, Robert, Danoy, Patrick, Griggs, Kim, Hewitt, Alex W., Landers, John, Mitchell, Paul, Mackey, David A. and Craig, Jamie E. (2012) Association of genetic variants in the TMCO1 gene with clinical parameters related to glaucoma and characterization of the protein in the eye. Investigative Ophthalmology and Visual Science, 53 8: 4917-4925.


Author Sharma, Shiwani
Burdon, Kathryn P.
Chidlow, Glyn
Klebe, Sonja
Crawford, April
Dimasi, David P.
Dave, Alpana
Martin, Sarah
Javadiyan, Shahrbanou
Wood, John P. M.
Casson, Robert
Danoy, Patrick
Griggs, Kim
Hewitt, Alex W.
Landers, John
Mitchell, Paul
Mackey, David A.
Craig, Jamie E.
Title Association of genetic variants in the TMCO1 gene with clinical parameters related to glaucoma and characterization of the protein in the eye
Journal name Investigative Ophthalmology and Visual Science   Check publisher's open access policy
ISSN 0146-0404
1552-5783
Publication date 2012-07
Sub-type Article (original research)
DOI 10.1167/iovs.11-9047
Volume 53
Issue 8
Start page 4917
End page 4925
Total pages 9
Place of publication Rockville, MD, United States
Publisher Association for Research in Vision and Ophthalmology
Collection year 2013
Language eng
Abstract Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma (POAG) is the most common subtype. We recently reported association of genetic variants at chromosomal loci, 1q24 and 9p21, with POAG. In this study, we determined association of the most significantly associated single nucleotide polymorphism (SNP) rs4656461, at 1q24 near the TMCO1 gene, with the clinical parameters related to glaucoma risk and diagnosis, and determined ocular expression and subcellular localization of the human TMCO1 protein to understand the mechanism of its involvement in POAG. Association of SNP rs4656461 with five clinical parameters was assessed in 1420 POAG cases using linear regression. The TMCO1 gene was screened for mutations in 95 cases with a strong family history and advanced disease. Ocular expression and subcellular localization of the TMCO1 protein were determined by immunolabeling and as GFP-fusion. The data suggest that individuals homozygous for the rs4656461 risk allele (GG) are 4 to 5 years younger at diagnosis than noncarriers of this allele. Our data demonstrate expression of the TMCO1 protein in most tissues in the human eye, including the trabecular meshwork and retina. However, the subcellular localization differs from that reported in other studies. We demonstrate that the endogenous protein localizes to the cytoplasm and nucleus in vivo and ex vivo. In the nucleus, the protein localizes to the nucleoli. This study shows a relationship between genetic variation in and around TMCO1 with age at diagnosis of POAG and provides clues to the potential cellular function/s of this gene.
Keyword Open-angle glaucoma
Nucleolin
Open Access Mandate Compliance Yes - Open Access (Publisher DOI)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print June 19, 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
 
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