Association between glaucoma and gene polymorphism of endothelin type A receptor.
OBJECTIVE
Endothelin 1 (ET-1), a potent vasoconstrictor, may affect regulation of intraocular pressure and ocular vessel tone. Thus, ET-1 and its receptors may contribute to development of glaucoma. We investigated whether gene polymorphisms of ET-1 (EDN1) and its receptors ETA (EDNRA) and ETB (EDNRB) were associated with glaucoma phenotypes and clinical features.


METHODS
We studied 224 normal Japanese controls and 426 open angle glaucoma (OAG) patients including 176 with primary open angle glaucoma (POAG) and 250 with normal tension glaucoma (NTG). Nine single nucleotide polymorphisms were detected among the participants using the Invader assay; four for EDN1 (T-1370G, +138/ex1 del/ins, G8002A, K198N), four for EDNRA (G-231A, H323H, C+70G, C+1222T), and one for EDNRB (L277L). Genotype distributions were compared between normal controls and OAG. Age at diagnosis, untreated maximum intraocular pressure (IOP), and visual field defects at diagnosis were examined for association with polymorphisms.


RESULTS
Of the 9 polymorphisms, genotype distributions showed no significant differences between OAG patients and controls adjusted by age. The GG genotype of EDNRA/C+70G was associated with worse visual field defects in NTG patients (p=0.014; Mann-Whitney U test, and p=0.027; logistic regression analysis).


CONCLUSIONS
The polymorphism of EDNRA/C+70G may be related to NTG risk factors.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. karin-i@sc.itc.keio.ac.jp
Karin
K
Ishikawa
Tomoyo
T
Funayama
Yuichiro
Y
Ohtake
Itaru
I
Kimura
Hidenao
H
Ideta
Kenji
K
Nakamoto
Noriko
N
Yasuda
Takeo
T
Fukuchi
Takuro
T
Fujimaki
Akira
A
Murakami
Ryo
R
Asaoka
Yoshihiro
Y
Hotta
Takashi
T
Kanamoto
Hidenobu
H
Tanihara
Koichi
K
Miyaki
Yukihiko
Y
Mashima
D000368:Aged; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044022:Receptor, Endothelin A / Q000235:genetics*; D044023:Receptor, Endothelin B / Q000235:genetics; D012307:Risk Factors; D014786:Vision Disorders / Q000503:physiopathology; D014794:Visual Fields
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B