LOXL1 genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population.
OBJECTIVE
We performed genetic association studies using a native Japanese population to examine the reproducibility of results of lysyl oxidase-like 1 (LOXL1) genetic association studies for exfoliation glaucoma (XFG) beyond the differences of ethnicity. We also quantified LOXL1 mRNA expression in the human lens capsule to examine the possible correlation between LOXL1 expression and XFG pathogenesis.


METHODS
We performed a case-control study using 95 Japanese XFG patients and 190 controls. Real-time polymerase chain reaction (PCR) analysis was performed using lens capsules obtained during surgery.


RESULTS
The TT genotype in the single nucleotide polymorphism (SNP) rs1048661 and the GG genotype in the SNP rs3825942 in exon 1 of LOXL1 were significantly associated with an increased risk of XFG under recessive models (chi(2) test, p=5.34 x 10(-34) and p=2.1 x 10(-8), respectively). Quantification of LOXL1 mRNA expression demonstrated no significant difference between XFG and senile cataract samples.


CONCLUSIONS
Although the functional effects of the LOXL1 SNP appear to be qualitative rather than quantitative, the amino acid substitution (R141L) caused by SNP rs1048661 is not a simple decisive factor for XFG due to the inverted allele frequency between Japanese XFG and Caucasian XFG patients. Further genetic and functional studies are essential for clarifying XFG pathogenesis.
Mori
Kazuhiko
K
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Imai
Kojiro
K
Matsuda
Akira
A
Ikeda
Yoko
Y
Naruse
Shigeta
S
Hitora-Takeshita
Hisako
H
Nakano
Masakazu
M
Taniguchi
Takazumi
T
Omi
Natsue
N
Tashiro
Kei
K
Kinoshita
Shigeru
S
D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D017889:Exfoliation Syndrome / Q000150:complications* / Q000235:genetics*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005901:Glaucoma / Q000150:complications / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007903:Lens Capsule, Crystalline / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human