An Investigation Into LOXL1 Variants in Black South African Individuals With Exfoliation Syndrome

Abstract

Objective: To investigate the association between 2 lysyl oxidase-like 1 (LOXL1) polymorphisms, rs1048661 (R141L) and rs3825942 (G153D), and exfoliation syndrome (XFS) in black South African individuals. Methods: A total of 43 black patients with XFS and 47 ethnically matched controls were recruited for genetic analysis. Samples were analyzed for presence of the LOXL1-R141L and G153D variants using restriction fragment length polymorphism analysis. A case-control association study was performed. Results: The R141L and G153D single-nucleotide polymorphisms (SNPs) were both significantly associated with XFS (P = .00582 and P Ͻ .00001, respectively). Consistent with findings in white populations but not in Asian cohorts, the GG genotype of the R141L SNP was present in significantly more XFS cases than controls (P=.00582). However, in this black South African study population, the AA genotype of G153D was present in an overwhelming majority of cases with XFS (P Ͻ .00001; odds ratio, 17.10; 95% confidence interval, 4.91-59.56), contrary to all previous articles in which the GG genotype was strongly associated with the disease phenotype. Conclusion: The LOXL1 SNPs R141L and G153D are significantly associated with XFS in this black South African population. The AA genotype of G153D confers XFS risk in this population, as opposed to the GG genotype described in all other populations, suggesting that unidentified genetic or environmental factors independent of these LOXL1 SNPs may influence phenotypic expression of the syndrome. Clinical Relevance: Elucidation of the role of genetic factors, including the LOXL1 gene, in XFS will facilitate identification of individuals predisposed to developing this condition.

Lysyl Oxidase–Like 1 Gene in the Reversal of Promoter Risk Allele in Pseudoexfoliation Syndrome

“…38 An uncommon phenomenon observed in the present study was that the A allele of rs16958477 showed a protective effect (P = 4.77 × 10 −6 ; OR, 0.50) in the South Indian cohort. This result is consistent with the recent genetic finding [23][24][25]28,29,34,35 on the reversal of risk alleles of 3 LOXL1 SNPs (rs1048661, rs3825942, and rs2165241). This unique observation suggests that rs16958477 might not be causative in PEX abnormalities and that the true functional variants are yet to be identified.…”

“…This SNP also showed significant deviation from HWE (P = 2 × 10 −5 ) in PEX cases in a previous study. 35 Strong asso- ; OR, 2.88) are the risk-associated alleles in this population (Table 1), which is similar to that found in the original study conducted in Icelandic and Swedish populations.…”

Lysyl Oxidase–Like 1 Gene in the Reversal of Promoter Risk Allele in Pseudoexfoliation Syndrome

“…38 An uncommon phenomenon observed in the present study was that the A allele of rs16958477 showed a protective effect (P = 4.77 × 10 −6 ; OR, 0.50) in the South Indian cohort. This result is consistent with the recent genetic finding [23][24][25]28,29,34,35 on the reversal of risk alleles of 3 LOXL1 SNPs (rs1048661, rs3825942, and rs2165241). This unique observation suggests that rs16958477 might not be causative in PEX abnormalities and that the true functional variants are yet to be identified.…”

“…This SNP also showed significant deviation from HWE (P = 2 × 10 −5 ) in PEX cases in a previous study. 35 Strong asso- ; OR, 2.88) are the risk-associated alleles in this population (Table 1), which is similar to that found in the original study conducted in Icelandic and Swedish populations.…”

Association of LOXL1 Gene Polymorphisms in Exfoliation Glaucoma Patients

“…Our study showed a correlation of two coding LOXL1 polymorphisms with XFS in an Iranian population for the first time. Our results appear to have considerable similarity to Caucasian populations (9, 26) and vary from Chinese (27), Japanese (13), Korean (28), and South African (29) populations.…”

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

“…Following the removal of duplicate articles and the screening process, 79 full-text articles were assessed for eligibility. Among these, 37 studies met the inclusion criteria and were included in the meta-analysis (Thorleifsson et al, 2007;Fingert et al, 2007;Fan et al, 2008;Hewitt et al, 2008;Fuse et al, 2008;Ozaki et al, 2008;Mossböck et al, 2008;Challa et al, 2008;Pasutto et al, 2008;Schlötzer-Schrehardt et al, 2008;Aragon-Martin et al, 2008;Yang et al, 2008;Hayashi et al, 2008;Tanito et al, 2008;Mabuchi et al, 2008;Mori et al, 2008;Ramprasad et al, 2008;Lee et al, 2009;Chen et al, 2009;Lemmelä et al, 2009;Wolf et al, 2010;AbuAmero et al, 2010;Williams et al, 2010;Mayinu & Chen et al, 2011;Malukiewicz et al, 2011;Sagong et al, 2011;Abu-Amero et al, 2011;Rautenbach et al, 2011;Jaimes et al, 2012;Micheal et al, 2012;Chiras et al, 2013;Metaxaki et al, 2013;Kasım et al, 2013;Park et al, 2013;Anastasopoulos et al, 2014;Dubey et al, 2014;de Juan-Marcos et al, 2014). In two of these studies (Thorleifsson et al, 2007;…”

Lysyl Oxidase–Like 1 Gene in the Reversal of Promoter Risk Allele in Pseudoexfoliation Syndrome

“…38 An uncommon phenomenon observed in the present study was that the A allele of rs16958477 showed a protective effect (P = 4.77 × 10 −6 ; OR, 0.50) in the South Indian cohort. This result is consistent with the recent genetic finding [23][24][25]28,29,34,35 on the reversal of risk alleles of 3 LOXL1 SNPs (rs1048661, rs3825942, and rs2165241). This unique observation suggests that rs16958477 might not be causative in PEX abnormalities and that the true functional variants are yet to be identified.…”

“…This SNP also showed significant deviation from HWE (P = 2 × 10 −5 ) in PEX cases in a previous study. 35 Strong asso- ; OR, 2.88) are the risk-associated alleles in this population (Table 1), which is similar to that found in the original study conducted in Icelandic and Swedish populations.…”

Association of LOXL1 Gene Polymorphisms in Exfoliation Glaucoma Patients

“…Our study showed a correlation of two coding LOXL1 polymorphisms with XFS in an Iranian population for the first time. Our results appear to have considerable similarity to Caucasian populations (9, 26) and vary from Chinese (27), Japanese (13), Korean (28), and South African (29) populations.…”

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

“…Following the removal of duplicate articles and the screening process, 79 full-text articles were assessed for eligibility. Among these, 37 studies met the inclusion criteria and were included in the meta-analysis (Thorleifsson et al, 2007;Fingert et al, 2007;Fan et al, 2008;Hewitt et al, 2008;Fuse et al, 2008;Ozaki et al, 2008;Mossböck et al, 2008;Challa et al, 2008;Pasutto et al, 2008;Schlötzer-Schrehardt et al, 2008;Aragon-Martin et al, 2008;Yang et al, 2008;Hayashi et al, 2008;Tanito et al, 2008;Mabuchi et al, 2008;Mori et al, 2008;Ramprasad et al, 2008;Lee et al, 2009;Chen et al, 2009;Lemmelä et al, 2009;Wolf et al, 2010;AbuAmero et al, 2010;Williams et al, 2010;Mayinu & Chen et al, 2011;Malukiewicz et al, 2011;Sagong et al, 2011;Abu-Amero et al, 2011;Rautenbach et al, 2011;Jaimes et al, 2012;Micheal et al, 2012;Chiras et al, 2013;Metaxaki et al, 2013;Kasım et al, 2013;Park et al, 2013;Anastasopoulos et al, 2014;Dubey et al, 2014;de Juan-Marcos et al, 2014). In two of these studies (Thorleifsson et al, 2007;…”

Lysyl Oxidase–Like 1 Gene in the Reversal of Promoter Risk Allele in Pseudoexfoliation Syndrome

“…38 An uncommon phenomenon observed in the present study was that the A allele of rs16958477 showed a protective effect (P = 4.77 × 10 −6 ; OR, 0.50) in the South Indian cohort. This result is consistent with the recent genetic finding [23][24][25]28,29,34,35 on the reversal of risk alleles of 3 LOXL1 SNPs (rs1048661, rs3825942, and rs2165241). This unique observation suggests that rs16958477 might not be causative in PEX abnormalities and that the true functional variants are yet to be identified.…”

“…This SNP also showed significant deviation from HWE (P = 2 × 10 −5 ) in PEX cases in a previous study. 35 Strong asso- ; OR, 2.88) are the risk-associated alleles in this population (Table 1), which is similar to that found in the original study conducted in Icelandic and Swedish populations.…”

Association of LOXL1 Gene Polymorphisms in Exfoliation Glaucoma Patients

“…Our study showed a correlation of two coding LOXL1 polymorphisms with XFS in an Iranian population for the first time. Our results appear to have considerable similarity to Caucasian populations (9, 26) and vary from Chinese (27), Japanese (13), Korean (28), and South African (29) populations.…”

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

“…Following the removal of duplicate articles and the screening process, 79 full-text articles were assessed for eligibility. Among these, 37 studies met the inclusion criteria and were included in the meta-analysis (Thorleifsson et al, 2007;Fingert et al, 2007;Fan et al, 2008;Hewitt et al, 2008;Fuse et al, 2008;Ozaki et al, 2008;Mossböck et al, 2008;Challa et al, 2008;Pasutto et al, 2008;Schlötzer-Schrehardt et al, 2008;Aragon-Martin et al, 2008;Yang et al, 2008;Hayashi et al, 2008;Tanito et al, 2008;Mabuchi et al, 2008;Mori et al, 2008;Ramprasad et al, 2008;Lee et al, 2009;Chen et al, 2009;Lemmelä et al, 2009;Wolf et al, 2010;AbuAmero et al, 2010;Williams et al, 2010;Mayinu & Chen et al, 2011;Malukiewicz et al, 2011;Sagong et al, 2011;Abu-Amero et al, 2011;Rautenbach et al, 2011;Jaimes et al, 2012;Micheal et al, 2012;Chiras et al, 2013;Metaxaki et al, 2013;Kasım et al, 2013;Park et al, 2013;Anastasopoulos et al, 2014;Dubey et al, 2014;de Juan-Marcos et al, 2014). In two of these studies (Thorleifsson et al, 2007;…”