Association of LOXL1 common sequence variants in German and Italian patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.
OBJECTIVE
Three common sequence variants in the lysyl oxidase-like 1 (LOXL1) gene were recently associated with both pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations from Iceland and Sweden. In this study, the genetic association of these variants was investigated in patients with PEX or PEXG of German and Italian descent.


METHODS
The three LOXL1 single-nucleotide polymorphisms (SNPs), one intronic (rs2165241) and two nonsynonymous coding SNPs (rs1048661: R141L and rs3825942: G153D) were genotyped in a total of 726 unrelated patients with PEX or PEXG (517 Germans and 209 Italians) and 418 healthy subjects who had normal findings in repeated ophthalmic examinations, and a genetic association study was performed.


RESULTS
Strong association with the three LOXL1 common sequence variants was seen in both the PEX and PEXG patient groups independent of their geographic origin (rs2165241, combined OR = 3.42, P = 1.28 x 10(-40); rs1048661, OR = 2.43, P = 2.90 x 10(-19); and rs3825942, OR = 4.87, P = 8.22 x 10(-23)). Similarly, the common frequent haplotype (G-G) composed of the two coding SNPs (rs1048661 and rs3825942) was strongly associated in PEX and PEXG cohorts of both populations with the disease (combined OR = 3.58, P = 5.21x 10(-43)).


CONCLUSIONS
Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independent of the presence of secondary glaucoma, confirming findings in patients from Northern Europe.
Pasutto
Francesca
F
Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Krumbiegel
Mandy
M
Mardin
Christian Y
CY
Paoli
Daniela
D
Lämmer
Robert
R
Weber
Bernhard H F
BH
Kruse
Friedrich E
FE
Schlötzer-Schrehardt
Ursula
U
Reis
André
A
D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D017889:Exfoliation Syndrome / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human