Ethnicity-based subgroup meta-analysis of the association of LOXL1 polymorphisms with glaucoma

Abstract

Purpose: To investigate the association and ethnic heterogeneity of lysyl oxidase-like 1 (LOXL1) single nucleotide polymorphisms (SNPs) with exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and other types of glaucoma.

Methods: We performed meta-analysis and ethnicity-based subgroup analyses according to published studies. Allele and genotype frequencies of SNPs rs1048661, rs2165241, and rs3825942 were extracted for analysis in Reviewer Manager: (1) comparison of the allelic distributions between XFS and XFG, (2) allelic association of LOXL1 SNPs with XFS/XFG, (3) associations in homozygote, heterozygote, and dominant and recessive models, and (4) allelic association with primary open angle glaucoma (POAG).

Results: In total 24 reported articles were retrieved, including Caucasian, African, Japanese, Indian, and Chinese populations. There was no significant difference in the distributions of rs1048661, rs2165241, and rs3825942 between XFS and XFG. The G allele of rs3825942 was the common at-risk allele for XFS/XFG in all populations with a total odds ratio (OR) of 10.89. The total homozygote OR of rs3825942 was 9.06 for XFS/XFG combined, but the total heterozygote OR was not significant. We also found that in the recessive model, the total OR was 14.70. There was no association of the three SNPs with POAG.

Conclusions: The association of rs3825942, but not rs2165241 or rs1048661, with XFS/XFG is consistent in different ethnic populations in the recessive model. LOXL1 is not associated with POAG in all study populations.

Figure 1

Meta-analysis of the distribution of single nucleotide polymorphism (SNP) rs1048661 between exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Meta-analysis indicated there is no statistical difference of distribution of the SNP rs1048661 G and T allele between XFS and XFG.

Figure 2

Meta-analysis of the distribution of single nucleotide polymorphism (SNP) rs2165241 between exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Meta-analysis indicated there is no statistical difference of distribution of the SNP rs2165241 T and C allele between XFS and XFG.

Figure 3

Meta-analysis of the distribution of single nucleotide polymorphism (SNP) rs3825942 between exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). Squares indicate study-specific risk difference (RD); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary RD with its corresponding 95% CI. Meta-analysis indicated there is no statistical difference of distribution of the SNP rs3825942 G and A allele between XFS and XFG.

Figure 6

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs3825942 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Subgroup meta-analysis indicated that the ORs SNP rs3825942 G allele is consistent in Caucasian and Japanese.

Figure 5

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs2165241 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Subgroup meta-analysis indicated that the ORs of SNP rs2165241 T allele are reversed in Caucasian and Japanese.

Figure 4

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs1048661 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Subgroup meta-analysis indicated that the ORs of SNP rs1048661 G allele are reversed in Caucasian and Japanese.

Figure 7

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs3825942 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in additive models. Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Synthesized homozygous OR (GG versus AA) of SNP rs3825942 was 9.06 for XFS/XFG.

Figure 8

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs3825942 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in additive models. Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Meta-analysis indicated that the heterozygote genotype (GA) does have higher susceptibility to XFS/XFG compared to AA genotype. C: Synthesized OR of SNP rs3825942 was 7.05 for XFS/XFG with dominant model (GG+GA versus AA).

Figure 9

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs3825942 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in dominant models. Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Synthesized OR of SNP rs3825942 was 7.05 for XFS/XFG with dominant model (GG+GA versus AA).

Figure 10

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs3825942 with a combined group of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in recessive models. Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Synthesized OR of SNP rs3825942 was 14.70 for XFS/XFG with recessive model (GG versus AA+GA).

Figure 11

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs1048661 with primary open angle glaucoma (POAG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Meta-analysis indicated there is no statistical significant association of SNP rs1048661 with POAG.

Figure 13

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs3825942 with primary open angle glaucoma (POAG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Meta-analysis indicated there is no statistical significant association of SNP rs3825942 with POAG.

Figure 12

Meta-analysis of the association of single nucleotide polymorphism (SNP) rs2165241 with primary open angle glaucoma (POAG). Squares indicate study-specific odds ratio (OR); the size of the box is proportional to the weight of the study; horizontal lines indicate 95% confidence interval (CI); diamond indicates summary OR with its corresponding 95% CI. Meta-analysis indicated there is no statistical significant association of SNP rs2165241 with POAG.