Dataset Information

Three Single Nucleotide Polymorphisms of LOXL1' in a Turkish Population with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.

ABSTRACT:

Objectives

To investigate the three single nucleotide polymorphisms (SNPs) (rs3825942, rs1048661, and rs2165241) of the LOXL1 gene in pseudoexfoliation syndrome (XFS) and pseudoexfoliation glucoma (XFG) in the Turkish population.

Materials and methods

DNA was obtained from blood samples of 48 XFS, 58 XFG, and 171 control subjects. Three LOXL1 SNPs (rs3825942, rs1048661, rs2165241) were investigated with real time PCR, a probe-based genotyping method, and melting curve analysis.

Results

All three SNPs of LOXL1 were significantly associated with XFS (rs3825942 p=3.54x10^-6, odds ratio [OR]=∞; rs1048661 p=0.008, OR=2.18; rs2165241 p=8.69x10^-9, OR=4.30) and XFG (rs3825942 p=3.41x10^-7, OR=∞; rs1048661 p=1.75x10^-5, OR=3.78; rs2165241 p=3.85x10^-11 OR=4.90). No significant differences were observed between the XFS and XFG groups for any of the SNPs. The GG genotype of rs3825942 was more valuable for distinguishing pseudoexfoliative cases from healthy individuals. The homozygous TT genotype of rs2165241 was associated with 6-fold increased XFS risk (p=8.15x10^-8, OR=6.32) and 7-fold increased XFG risk (p=1.45x10^-10 OR=7.95). The GGT haplotype consisting of all three risk alleles was associated with a 7.45-fold higher risk of XFS/XFG (p=8.65x10^-14, OR=7.45). Presence of T allele of rs2165241 conferred 3 times higher risk for men than women (p=6.78x10^-5, OR=3.202).

Conclusion

LOXL1 SNPs are associated with increased risk for pseudoexfoliation in the Turkish population. T allele of rs2165241 was found to be the most important characterized risk factor for our cohort. All SNP distributions were similar to other European and American populations.

SUBMITTER: Yaz Y

PROVIDER: S-EPMC6216538 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Three Single Nucleotide Polymorphisms of <i>LOXL1</i>' in a Turkish Population with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.

Yaz Yetkin Y Yıldırım Nilgün N Aydın Yaz Yasemin Y Çilingir Oğuz O Yüksel Zafer Z Mutlu Fezan F

Turkish journal of ophthalmology 20181031 5

<h4>Objectives</h4>To investigate the three single nucleotide polymorphisms (SNPs) (rs3825942, rs1048661, and rs2165241) of the <i>LOXL1</i> gene in pseudoexfoliation syndrome (XFS) and pseudoexfoliation glucoma (XFG) in the Turkish population.<h4>Materials and methods</h4>DNA was obtained from blood samples of 48 XFS, 58 XFG, and 171 control subjects. Three <i>LOXL1</i> SNPs (rs3825942, rs1048661, rs2165241) were investigated with real time PCR, a probe-based genotyping method, and melting curv ...[more]

PMID: 30405941

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Project description:PurposeTo study lysyl oxidase-like 1 (LOXL1) expression in freshly collected lens capsules from pseudoexfoliation syndrome (XFS), pseudoexfoliation glaucoma (XFG), and normal cataract control individuals. We also investigated the effects of four glaucoma drug medications on LOXL1 expression in primary human lens epithelial cell cultures to see if they could affect LOXL1 expression.MethodsLens capsules were collected at the time of cataract surgery. Controls were matched to age, sex, and ethnicity. Total RNA was isolated from individual lens capsule samples and real-time PCR was performed on each sample using primers flanking the sixth exon of the LOXL1 gene. Cell cultures were grown to confluence in four separate six-well plates at 37 °C in 5% CO2. Each plate was then treated with one of four different glaucoma drugs (brinzolamide 1%, brimonidine tartrate 0.1%, timolol maleate 0.5%, and latanoprost 0.005%) once daily for seven days (at both 1:1,000 and 1:100 concentrations relative to media). Controls were not treated with any drug but media was changed in the same manner. After one week of treatment, cells were harvested and total RNA isolated. Real-time PCR was performed on each group of cells.ResultsSeven XFS, seven XFG, and ten cataract control specimens were analyzed. LOXL1 expression was detected in the lens capsule specimens from each of the four groups. Significant expression differences were found between the control and XFG groups and XFS and XFG groups. No significant difference was observed between the control and XFS group. No significant decrease in LOXL1 expression was seen with drug incubation of the four medications (Brinzolamide, Timolol, Latanoprost, and Brimonidine) at the 1:1,000 drug:media concentrations versus controls. At 10-fold higher concentrations (1:100 drug:media), brinzolamide, timolol maleate, and latanoprost showed small increases in LOXL1 expression relative to controls. This effect was not observed with brimonidine tartrate.ConclusionsThese results establish that LOXL1 expression is reduced in lens capsule specimens from XFG individuals but not XFS. The drug treatment incubation studies suggest that the change in LOXL1 expression observed in XFG is not attributable to glaucoma drug therapy. If a causative functional relationship can be validated, modification of LOXL1 expression in affected tissues may represent a novel treatment strategy for this disorder.

Project description:PURPOSE: Single nucleotide polymorphisms (SNPs) within the lysyl oxidase like-1 gene (LOXL1; rs1048661 and rs3825942) were found to confer risk to pseudoexfoliation glaucoma (XFG) through the pseudoexfoliation syndrome (XFS) in Nordic, Caucasian, and two Asiatic populations (Indian and Japanese). The prevalence (0.2%-0.7%) of XFS in the Chinese is considerably lower compared to Nordic populations. The aim of this study was to determine the association of LOXL1 in Chinese subjects with XFS/XFG. METHODS: Chinese subjects with clinically diagnosed XFS/XFG and normal controls were recruited. Genomic DNA was extracted, and the two LOXL1 SNPs (rs1048661 and rs3825942) were genotyped by bidirectional sequencing. Allele and genotype frequencies were compared between cases and unrelated controls using PLINK. Linkage disequilibrium (LD) calculations and haplotype association analysis were done using the Haploview package and WHAP package, respectively. RESULTS: Sixty-two Chinese patients (17 XFG and 45 XFS) and 171 Chinese controls were studied. The G allele of LOXL1 SNP rs3825942 was moderately associated (OR=10.97, p=0.0018) with pseudoxfoliation in the Chinese. The frequency of the G allele of rs1048661 was not significantly different in cases compared to controls (p=0.142) in the allelic association test. However, the genotype test showed marginal association for rs1048661 (p=0.030). Only three haplotypes were observed (T-G, G-G, and G-A) with G-G as a risk haplotype (p=0.0034) and G-A as a protective haplotype (p=0.00039). T-G, which was a risk haplotype in the Japanese, was not associated with XFG in the Chinese (p=0.124). CONCLUSIONS: Polymorphisms in LOXL1 confer risk to XFS/XFG in the Chinese. The lower incidence of XFS compared to other populations suggests additional genetic or environmental factors to have a major influence on the phenotypic expression of XFS in the Chinese. The G allele of rs3825942 has been shown to be associated with XFS/XFG in all populations studied to date.