Different WDR36 mutation pattern in Chinese patients with primary open-angle glaucoma.
OBJECTIVE
To determine the distribution of WD repeat domain 36 (WDR36) sequence variants in Chinese patients with primary open-angle glaucoma (POAG).


METHODS
One hundred and thirty-five unrelated POAG patients (82 high tension glaucoma [HTG], 42 normal tension glaucoma [NTG], and 11 juvenile-onset POAG [JOAG] patients) and 77 unrelated controls were recruited. All 23 coding exons and splicing junctions of WDR36 were sequenced using BigDye Terminator v3.1 cycle sequencing kit. Single nucleotide polymorphism (SNP) and haplotype associations were analyzed using PLINK (version 1.04).


RESULTS
Nineteen sequence alterations were identified, and eight of them were novel including two novel nonsynonymous SNPs (L240V and I713V). Except the common I264V polymorphism, no other previously reported disease-causing or disease-susceptibility mutations were found. The novel I713V mutation was observed in three (3.7%) patients with HTG. One intronic SNP, IVS5+30C>T (rs10038177), showed significantly higher frequency of minor allele T in HTG patients (16.5%) than in controls (1.3%; Odds ratio [OR]=15.0, p=7.9 x 10(-7), Bonferroni corrected p=1.5 x 10(-5)). Haplotype GTA, which is composed of rs13153937, rs10038177, and rs11241095, was significantly associated with HTG (OR=22.5, p=0.002, Bonferroni corrected p=0.013). Neither the individual SNPs nor haplotypes of WDR36 were associated with NTG or JOAG (Bonferroni corrected p>0.05).


CONCLUSIONS
Findings in this study suggest WDR36 to be associated with sporadic HTG but not with NTG or JOAG. Our results also suggest a different mutation pattern of WDR36 in the Chinese population from other ethnic populations.
Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
Bao Jian
BJ
Fan
Dan Yi
DY
Wang
Ching-Yu
CY
Cheng
Wendy Charles
WC
Ko
Shun Chiu
SC
Lam
Chi Pui
CP
Pang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003710:Demography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
D005136:Eye Proteins; C502341:WDR36 protein, human