TY - JOUR
T1 - EAAT1 variants associated with glaucoma
AU - Yanagisawa, Michiko
AU - Namekata, Kazuhiko
AU - Aida, Tomomi
AU - Katou, Sayaka
AU - Takeda, Takuya
AU - Harada, Takayuki
AU - Fuse, Nobuo
AU - the Glaucoma Gene Research Group, Glaucoma Gene Research Group
AU - Tanaka, Kohichi
N1 - Funding Information:
This work was supported by Strategic Research Program for Brain Sciences (SRPBS) from Ministry of Education, Culture, Sports, Science and Technology of Japan (to K.T.), the grant from Japan Society for the Promotion of Science (to K.N. and T.H.), the Ministry of Health, Labor and Welfare of Japan (to T.H., N.F., and K.T.), Suzuken Memorial Foundation (to T.A.) and the Joint Usage/Research Program of Medical Research Institute, Tokyo Medical and Dental University (to T.H., T.A. and K.T.).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/3
Y1 - 2020/9/3
N2 - Glaucoma is one of the leading causes of blindness characterized by progressive loss of retinal ganglion cells (RGCs) and their axons. We reported that glutamate/aspartate transporter (GLAST) knockout mice showed progressive RGC loss and optic nerve degeneration that are similar to glaucoma. To explore the possibility that rare variants in the EAAT1 gene (the human homolog of GLAST) cause susceptibility to glaucoma, we performed targeted sequencing of EAAT1 in 440 patients with glaucoma and 450 control subjects. We identified 8 rare variants in 20 out of 440 patients, including 4 synonymous and 4 missense variants located at protein coding regions. One of these rare variants (rs117295512) showed significant association with the risk of glaucoma (OR = 10.44, P = 0.005). Furthermore, the allele frequency for loss-of-function EAAT1 variants, pAla169Gly and pAla329Thr, was 5.5 folds higher in the glaucoma (1.1%) compared with the control cohort (0.2%). These findings suggest that these rare variants may contribute to the pathogenesis of glaucoma and that loss-of-function variants in EAAT1 are present in a small number of patients with glaucoma.
AB - Glaucoma is one of the leading causes of blindness characterized by progressive loss of retinal ganglion cells (RGCs) and their axons. We reported that glutamate/aspartate transporter (GLAST) knockout mice showed progressive RGC loss and optic nerve degeneration that are similar to glaucoma. To explore the possibility that rare variants in the EAAT1 gene (the human homolog of GLAST) cause susceptibility to glaucoma, we performed targeted sequencing of EAAT1 in 440 patients with glaucoma and 450 control subjects. We identified 8 rare variants in 20 out of 440 patients, including 4 synonymous and 4 missense variants located at protein coding regions. One of these rare variants (rs117295512) showed significant association with the risk of glaucoma (OR = 10.44, P = 0.005). Furthermore, the allele frequency for loss-of-function EAAT1 variants, pAla169Gly and pAla329Thr, was 5.5 folds higher in the glaucoma (1.1%) compared with the control cohort (0.2%). These findings suggest that these rare variants may contribute to the pathogenesis of glaucoma and that loss-of-function variants in EAAT1 are present in a small number of patients with glaucoma.
KW - EAAT1
KW - Excitotoxicity
KW - Glaucoma
KW - Glutamate transporter
KW - Missense mutation
KW - Retina
UR - http://www.scopus.com/inward/record.url?scp=85088799218&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088799218&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.06.099
DO - 10.1016/j.bbrc.2020.06.099
M3 - Article
C2 - 32819603
AN - SCOPUS:85088799218
SN - 0006-291X
VL - 529
SP - 943
EP - 949
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -