Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and northern Chinese.
OBJECTIVE
The lysyl oxidase-like protein 1 (LOXL1) gene is strongly associated with exfoliation glaucoma, which is very rare in the Chinese population. The implicated LOXL1 polymorphisms have not been associated with primary open-angle glaucoma (POAG). In this study, we investigated three of the LOXL1 polymorphisms in POAG in a southern Chinese population of Hong Kong and northern Chinese from Beijing.


METHODS
The Hong Kong group included 293 POAG patients and 250 controls, and the Beijing group included 169 POAG patients and 197 controls. LOXL1 single nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, were genotyped by direct DNA sequencing. Individual association was analyzed using the chi(2) test, and haplotype-based association analysis was performed in WHAP.


RESULTS
Each of the candidate SNPs was not statistically associated with POAG in either group (p>0.017, Bonferroni correction). Haplotype-based association analysis had identified a significant omnibus association (Omnibus chi(2)=18.16, p=0.00115) between these SNPs and POAG in the Hong Kong group. A minor haplotype (T-G-T) showed significant statistical association with POAG. It presented in 2.1% of cases and 0.4% of controls, conferring a 5.24 fold of increased risk to the disease (95% CI: 1.17-23.54, P(perm)=0.00108). However, this haplotype was absent in the Beijing group.


CONCLUSIONS
Individual LOXL1 SNPs, rs1048661, rs3825942, and rs2165241, were not associated with POAG in the Chinese population. However, a minor haplotype T-G-T was found to be associated with the disorder in the southern Chinese. The low frequencies of the at-risk alleles at rs1048661 and rs2165241 may be one of the factors that led to the low prevalence of exfoliation syndrome in the general populations of the Chinese.
Gong
Wei Fen
WF
Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
Chiang
Sylvia W Y
SW
Chen
Li Jia
LJ
Tam
Pancy O S
PO
Jia
Li Yun
LY
Leung
Dexter Y L
DY
Geng
Yi Qun
YQ
Tham
Clement C Y
CC
Lam
Dennis S C
DS
Ritch
Robert
R
Wang
Ningli
N
Pang
Chi Pui
CP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D003710:Demography; D005260:Female; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006239:Haplotypes; D006723:Hong Kong; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human