Dataset Information

LOXL1 gene polymorphism candidates for exfoliation glaucoma are also associated with a risk for primary open-angle glaucoma in a Caucasian population from central Russia.

ABSTRACT:

Purpose

This study was aimed to replicate the previously reported associations of the three LOXL1 gene polymorphisms with exfoliation glaucoma (XFG) and to analyze these genetic variants for their possible contribution to primary open-angle glaucoma (POAG) in Caucasians from central Russia.

Methods

In total, 932 participants were recruited for the study, including 328 patients with XFG, 208 patients with POAG, and 396 controls. The participants were of Russian ethnicity (self-reported) and born in Central Russia. They were genotyped at three single nucleotide polymorphisms (SNPs) of the LOXL1 gene (rs2165241, rs4886776, and rs893818). The association was analyzed using logistic regression.

Results

Allele C of rs2165241 was associated with a decreased risk of XFG (odds ratio [OR] =0.27-0.45, p_perm ≤5*10^-6) and POAG (OR=0.35-0.47, р_perm≤0.001), and allele A of rs4886776 and rs893818 were associated with a lower risk of XFG (OR=0.53-0.57, р_perm≤0.001). Haplotype TGG of loci rs2165241-rs4886776-rs893818 was associated with an elevated risk of XFG (OR=2.23, р_perm=0.001) and POAG (OR=2.01, р_perm=0.001), haplotype CGG was also associated with a decreased risk of XFG (OR=0.45, р_perm=0.001) and POAG (OR=0.35, р_perm=0.001). Haplotype CAA was associated with a decreased risk of XFG only (OR=0.50, р_perm=0.001).

Conclusions

Polymorphisms rs2165241, rs4886776, and rs893818 of the LOXL1 gene showed association with XFG and POAG in a Caucasian sample from central Russia.

SUBMITTER: Eliseeva N

PROVIDER: S-EPMC8116259 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE: Single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). We have shown that these SNPs are not associated with the primary glaucomas such as primary open-angle (POAG) glaucoma and primary angle-closure glaucoma (PACG). To further establish the specificity of LOXL1 SNPs for XFS and XFG, we determined whether these SNPs were involved in pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). METHODS: Three SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were screened in a cohort of 78 unrelated and clinically well characterized glaucoma cases comprising of PG (n=44) and PDS (n=34) patients as well as 108 ethnically matched normal controls of Caucasian origin. The criteria for diagnosis of PDS/PG were Krukenberg spindle, hyperpigmentation of the trabecular meshwork, and wide open angle. Transillumination defects were detected by infrared pupillography, and the presence of a Zentmayer ring was considered as a confirmatory sign. All three SNPs were genotyped in cases and controls by resequencing the genomic region of LOXL1 harboring these variants and were further confirmed by polymerase chain reaction (PCR)-based restriction digestions. Haplotypes were generated from the genotype data, and the linkage disequilibrium (LD) and haplotype analysis were done with Haploview software that uses the expectation maximization (EM) algorithm. RESULTS: The LOXL1 SNPs showed no significant association with PDS or PG. There was no significant difference in the frequencies of the risk alleles of rs1048661 ('G' allele; p=0.309), rs3825942 ('G' allele' p=0.461), and rs2165241 ('T' allele; p=0.432) between PG/PDS cases and controls. Similarly, there was no involvement of the XFS/XFG-associated haplotypes, 'G-G' (p=0.643; [OR=1.08, 95%CI, 0.59-1.97]) and 'T-G' (p=0.266; [OR=1.35, 95%CI, 0.70-2.60]), with the PDS/PG phenotypes. The risk haplotype 'G-G' was observed in ~55% of the normal controls. CONCLUSIONS: There was no involvement of the LOXL1 SNPs in patients with PDS and PG. The results further indicate that the associations of these SNPs are specific to XFS/XFG.