Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese.
OBJECTIVE
To determine whether mutations in the WD repeat domain 36 gene (WDR36) are associated with primary open-angle glaucoma (POAG) in Japanese. Subjects with high tension glaucoma (HTG) and normal tension glaucoma (NTG) were analyzed separately.


METHODS
One hundred and thirty-six unrelated Japanese patients with HTG and 103 unrelated patients with NTG were studied. Genomic DNA was extracted from peripheral blood leukocytes, and all 23 exons were amplified by polymerase chain reaction (PCR) and directly sequenced bidirectionally.


RESULTS
Twenty sequence alterations were identified: 10 have already been reported (p.I264V, c.1494+90C>T, c.1494+143A>G, c.1609+89G>A, c.1775+89C>A, c.1965-30A>G, p.V714V, c.2170+217C>T, p.V727V, and c.2518+60G>C) and 10 were novel (p.D179D, p.Q270Q, p.M283R, c.898+63C>G, c.1074+20C>T, p.G459G, c.1884+26C>G, p.S664L, p.S664S, and p.P744P). One nonsynonymous amino acid change in exon 17, p.S664L, was identified in a patient with HTG. The frequency of the p.I264V variant was significantly higher in the HTG group than in the control group (p=0.01), but the frequency in the NTG group was not significantly different from the control group (p=0.12). The frequency of the c.1965-30A>G variant was also significantly higher in the HTG group than in the control group (p=0.03), but the frequency in the NTG group was not significantly different from the control group (p=0.06).


CONCLUSIONS
One nonsynonymous variant, p.S664L, and the association of the allelic variants (p.I264V and c.1965-30A>G) in WDR36 and their prevalence in unrelated Japanese patients with HTG suggest that they are probably involved in the pathogenesis of HTG.
Miyazawa
Akiko
A
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi, Japan.
Fuse
Nobuo
N
Mengkegale
MingGe
M
Ryu
Morin
M
Seimiya
Motohiko
M
Wada
Yuko
Y
Nishida
Kohji
K
D000368:Aged; D044466:Asian People / Q000235:genetics*; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics*; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D014794:Visual Fields
D005136:Eye Proteins; C502341:WDR36 protein, human; D004247:DNA