Lysyl Oxidase-like 1 Research Articles

The pathophysiology of pseudoexfoliation syndrome is affected by interaction of TGF‐β1 and LOXL1

PurposeThe cross‐linking enzyme lysyl oxidase‐like 1 (LOXL1) and profibrotic transforming growth factor (TGF)‐ß1 play key roles in pathophysiology of pseudoexfoliation (PEX) syndrome/glaucoma. The purpose of this study was to investigate the interaction between LOXL1 and TGF‐ß1 with respect to the PEX‐specific disordered matrix metabolism.MethodsPrimary human Tenon's capsule fibroblasts (hTCF) obtained from patients were treated with TGF‐ß1 (0‐10 ng/ml) for 12‐72 hours without or with preincubation with inhibitors of TGF‐β signalling pathways. Expression of LOXL1 and PEX‐specific extracellular matrix components was examined by using quantitative RT‐PCR and Western immunoblot analysis. Direct binding of LOXL1 to TGF‐ß1 was analyzed by blot overlay assay and solid phase ELISA using purified LOXL1, recombinant human TGF‐ß1, TGFß1‐LAP. The effect of LOXL1 on TGF‐ß1 signaling was analyzed using TGF‐ß receptor signaling real time PCR assays (BioRad) after transient transfection of hTCF with a full‐length pCMV6‐LOXL1 vector construct/with empty vector .ResultsTGFß1 significantly increased LOXL1 expression, secretion and enzymatic activity and correlated with enhanced expression of BMP‐1, elastin, fibrillin‐1, fibulin‐4 and fibulin‐5 with peak effects at 10 ng/ml for 48 hours. This induction was blocked by TGF‐β receptor inhibitors and inhibitors of the canonical Smad and non‐canonical signaling pathways. Direct binding between LOXL1 and TGFß1‐LAP was demonstrated by Blot overlay assays and ELISA. LOXL1 overexpression temporarily upregulates different transcriptional regulators and some protein kinases of p38‐MAPK signalling pathway after 12 to 24 hours post‐transfection.ConclusionsThe results of this study indicate that the interaction of LOXL1 and TGF‐ß1 plays an important role in the PEX‐associated abnormal matrix metabolism and fibrosis.

LOXL1 Hypermethylation in Pseudoexfoliation Syndrome in the Uighur Population.

High prevalence of pseudoexfoliation syndrome (PEX) occurs in the Uighur population. This study investigated DNA methylation of the lysyloxidase-like 1 (LOXL1) gene in Uighur PEX patients with cataracts. The research involved 10 lens capsule specimens from Uighur PEX patients with cataracts and 10 lens capsule specimens from Uighur control patients with age-related cataract (ARC) alone. All specimens were freshly collected during cataract surgery. Methylation status of the CpG islands was analyzed using pyrosequencing. The mRNA levels of LOXL1 were evaluated by quantitative real-time PCR, and protein levels were evaluated by Western blot assay. For all the six chosen CpG islands of the LOXL1 gene promoter, hypermethylation was found in the PEX with cataracts compared to the age-matched ARC group. At the same time, the expression level of LOXL1 mRNA was significantly reduced in the PEX with cataracts group than that in the ARC group, and the expression level of the LOXL1 protein product demonstrated a similar tendency. The susceptible PEX gene LOXL1 undergoes DNA hypermethylation in its promoter region in Uighur PEX with cataracts patients. This indicates that epigenetic regulation might play roles in PEX pathogenesis.

LOXL1 gene variants and their association with pseudoexfoliation glaucoma (XFG) in Spanish patients.

BackgroundLOXL1 gene is the most important genetic risk factor known so far for pseudoexfoliation glaucoma (XFG). Our purpose was to evaluate the potential association of individual genetic variants of the lysyl oxidase-like 1 (LOXL1) gene and haplotypes with XFG in Spanish patients.MethodsBlood samples were collected from a total of 105 Spanish patients with XFG and 200 healthy controls. The entire LOXL1 gene along with the promoter, coding and non-coding regions including the 5´- and 3´-untranslated regions, were sequenced using next-generation sequencing in 99 XFG patients. SNPs rs16958477 (promoter), rs1048661 (exon 1), rs3825942 (exon 1), rs2165241 (intron 1) and rs3522 (exon 7) in LOXL1 were genotyped by restriction fragment-length polymorphism (RFLP) in all Spanish control participants and in six additional XFG patients, and a case–control association study was performed.Comparisons of the allelic and genotypic frequencies were performed using standard χ2 test with Bonferroni and Pearson corrections. Logistic regression analyses were permormed using Sigmaplot v11. Haplotypes frequencies were performed using HaploView 4.0.ResultsSequencing of the LOXL1 gene in XFG participants identified a total of 212 SNPs, of which 49 exhibited allelic frequencies with significant differences between cases and controls, and 66 were not previously described. The allele frequencies of SNPs rs16958477, rs1048661, rs3825942, rs2165241, were significantly associated with an increased risk for XFG, however the SNP rs3522 was not.The haplotype frequencies of SNPs rs16958477, rs1048661, rs3825942 and rs2165241 and their association with XFG indicated that the CGGT haplotype, containing all four risk alleles, and the AGGT haplotype, which carries the protective allele of rs16958477 and three risk alleles of the other three SNPs, were significantly associated with XFG (p = 4.5×10−6, and p = 8.8×10−6), conferring more than 2-fold increased disease susceptibility.ConclusionsSNPs of the LOXL1 gene are associated with XFG in the Spanish population. This information adds new support to the distinct risk association frequencies of LOXL1 alleles with XFG in Western European and Asian populations. Identification and validation of additional SNPs along the entire LOXL1 gene of XFG cases may provide insightful information on their potential role in the pathogenesis of this disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0221-y) contains supplementary material, which is available to authorized users.

Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus.

Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (∼40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis.

Advances in molecular genetics of exfoliation syndrome

Exfoliation syndrome (XFS), one of the most common causes of glaucoma, represents an age related, complex, multifactorial and late-onset disease worldwide. The etiopathogenesis involves both genetic and environmental factor. However, the exact etiopathogenesis of XFS is still unclear. The purpose of this review was to discuss the recent research progress of the molecular genetics of XFS. Some candidate genes linked to XFS include lysyl oxidase-like 1 (LOXL1) gene, clusterin (CLU)gene, contactin associated protein-like 2 (CNTNAP2) gene, apolipoprotein E (ApoE) gene, matrix metallo proteinases (MMPs) gene, glutathione S-transferase (GST) gene, transforming growth factor-β1(TGF-β1) gene, tumor necrosis factor-α (TNF-α)gene and so on. These genes may be modifying genes for the development of XFS. Key words: Exfoliation syndrome; Molecular genetics; Gene

Ocular Pseudoexfoliation Syndrome and Life Span: Act 2

Ocular Pseudoexfoliation Syndrome and Life Span: Act 2

802 Increased Expression of Lysyl Oxidase-Like 2 (LOXL2) Is Found in Hepatic Tissue of Children With Biliary Atresia

802 Increased Expression of Lysyl Oxidase-Like 2 (LOXL2) Is Found in Hepatic Tissue of Children With Biliary Atresia

Update on pseudoexfoliation syndrome pathogenesis and associations with intraocular pressure, glaucoma and systemic diseases.

Pseudoexfoliation (PEX) syndrome is a common age-related disorder affecting intraocular and extraocular tissues. This review focuses on recent publications related with the pathogenesis and associations of PEX syndrome with intraocular pressure (IOP), glaucoma and systemic diseases. In PEX tissues, expression of lysyl oxidase-like 1 (LOXL1) was found to be markedly dysregulated. This may adversely affect elastin metabolism and lead to elastotic alteration in tissues such as lamina cribrosa. There is increasing evidence that cellular stress conditions and low-grade chronic inflammatory processes are involved in the pathogenesis of PEX. Although there is an increased risk for glaucoma development in patients with PEX and ocular hypertension as compared with non-PEX patients with ocular hypertension, LOXL1 single nucleotide polymorphisms were not associated with intraocular pressure (IOP) differences. Lack of association of PEX with all-cause mortality or dementia has been reported recently. The association with vascular diseases is not consistent among different studies. Despite the high prevalence of the LOXL1 variants in the general population, a much lower proportion of the population develops PEX, suggesting that in addition to LOXL1, other genetic, epigenetic and environmental factors may contribute to the development of PEX. Also, LOXL1 cannot help to identify those with PEX at increased risk for glaucoma development. Increased risk for glaucoma development in PEX patients who present with increased IOP may be related to other factors beyond IOP, contributing to increased vulnerability of the optic nerve to glaucoma development in the presence of PEX.

The association of LOXL1 polymorphisms with exfoliation syndrome/glaucoma: Meta-analysis.

To investigate the association of lysyl oxidase-like 1 (LOXL1) single nucleotide polymorphisms (SNPs) with exfoliation syndrome (XFS)/exfoliation glaucoma (XFG). Published manuscripts from PubMed and EMBASE were identified until May 2014. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for LOXL1 (rs1048661, rs2165241 and rs3825942) polymorphisms and the risk of XFS/XFG were estimated using random- or fixed- effect model. The three LOXL1 polymorphisms (rs1048661, rs3825942, and rs2165241) were associated with an increased risk for XFS/XFG among Caucasians, with OR 2.19(1.96-2.45), 8.8 (6.05-12.79) and 3.41 (3.11-3.73), respectively. On the contrast, the rs1048661 and rs2165241, but not rs3825942 polymorphism, have a potential protective effect on XFS/XFG in Asians, with OR 0.06 (0.02-0.18), 0.15 (0.09-0.25), respectively. There is strong evidence that LOXL1 polymorphisms are associated with XFS/XFG risk. The strength of risk might be ethnicity-dependent.

Association between LOXL1 gene polymorphisms and primary open angle glaucoma in Sichuan population

To investigate association between the lysyl oxidase-like 1 (LOXL1) gene single nucleotide polymorphism (SNP) and primary open-angle glaucoma (POAG) in Sichuan population. In this study,416 subjects with primary open-angle glaucoma and 997 normal controls were recruited.Three reported LOXL1 tag SNPs (rs1048661,rs3825942 and rs2165241) were genotyped by SNaPshot method. The study showed that the genotypes of LOXL1 rs1048661,rs3825942 and rs2165241 between POAG and control groups were not statistically significant (OR=1.085, 95%CI 0.92-1.28, P=0.578 for rs1048661; OR=1.059, 95%CI 0.82-1.37, P=0.846 for rs3825942; OR=1.006, 95%CI 0.77-1.32, P=0.966 for rs2165241, respectively). There were no significant difference in allele frequency distribution of LOXL1 rs1048661、rs3825942 and rs2165241 between POAG and normal controls (P=0.322, P=0.660, P=0.965). The results from the present study do not indicate the association of LOXL1 SNPs (rs1048661, rs3825942 and rs2165241) with POAG in Sichuan population.

Screening of lysyl oxidase (LOX) and lysyl oxidase like (LOXL) enzyme expression and activity in preterm prelabor rupture of fetal membranes.

Lysyl oxidase (LOX) and LOX like enzymes (LOXL1-4) physiologically remodel extracellular matrix and pathologically contribute to cellular senescence under oxidative stress (OS). We characterized LOX and LOXL expressions and activity in human fetal membranes. Human fetal membranes from women with uncomplicated pregnancies at term, preterm birth with intact membranes (PTB) or preterm prelabor rupture of membranes (pPROM), and in vitro fetal membranes stimulated with water-soluble cigarette smoke extract (CSE), an OS inducer, were analyzed by real-time PCR and immunohistochemistry for LOX and LOXL (1-4) expression and localization. LOX activity was measured by fluorometric assay. LOX gene expression was ∼2.5-fold higher in fetal membranes from pPROM compared to PTB and term (P=0.02). LOX and LOXL1, 2 and 4 were localized to both amniotic and chorionic cells, whereas LOXL3 was limited to chorion. LOX and LOXL isoform expressions were not different between CSE treated and untreated groups, while LOX activity was increased in the presence of an antioxidant (P=0.02). Increase of LOX expression in pPROM, an OS-related disease, and the apparent inhibition of LOX activity by CSE restored by antioxidant treatment suggest that reactive oxygen species might influence LOX-mediated tissue remodeling in fetal membranes. Balanced antioxidant supplementation during pregnancy may reduce the risk of pPROM by increasing LOX activity.

A peptide antagonist of thrombospondin-1 promotes abdominal aortic aneurysm progression in the angiotensin II-infused apolipoprotein-E-deficient mouse.

Interaction of the activating sequence in thrombospondin-1 (TSP-1) with the conserved sequence (leucine-serine-lysine-leucine [LSKL]) in the latency-associated peptide region of latent transforming growth factor (TGF)-β complex is important in regulating TGF-β1 activity. We aimed to assess the effect of blocking peptide LSKL on the progression of pre-established abdominal aortic aneurysm in angiotensin II-infused apolipoprotein E-deficient (ApoE(-/-)) mice. Abdominal aortic aneurysm was established in 3-month-old male ApoE(-/-) mice with subcutaneous infusion of angiotensin II for 28 days. After this, mice received LSKL peptide or control SLLK (serine-leucine-leucine-lysine) peptide (4 mg/kg) via daily intraperitoneal injection for an additional 2 weeks. Administration of LSKL peptide promoted larger suprarenal aortic diameter, as determined by ultrasound and morphometric analysis, and stimulated more severe atherosclerosis within the aortic arch. In addition, mice receiving LSKL peptide exhibited elevated circulating proinflammatory cytokine levels and greater inflammatory cells within the suprarenal aorta compared with controls. Mice receiving LSKL peptide showed low plasma TGF-β1 activity and low levels of aortic tissue phosphorylated to total Smad2/3. Aortic gene expression of TGF-β receptor 1 (TGFBRI) and receptor 2 (TGFBRII), but not TGF-β1 and thrombospondin-1, were lower in mice receiving LSKL peptide than controls. LSKL peptide administration was associated with greater aortic elastin fragmentation and lower expression and activity of the TGF-β1-target gene lysyl oxidase like 1 (LOXL1). Attenuation of thrombospondin-1-directed activation of TGF-β1 promotes abdominal aortic aneurysm and atherosclerosis progression in the angiotensin II-infused ApoE(-/-) mouse model.

Mutation screen of LOXL1 in patients with female pelvic organ prolapse.

The LOXL1 (lysyl oxidase-like 1) gene encodes a copper-dependent monoamine oxidase that catalyzes the deamination of a lysine residue in the cross-linking of tropoelastin monomers to form elastin. LOXL1-KO mice do not deposit normal elastic fibers in their genitourinary tract resulting in postpartum pelvic organ prolapse and lower urinary tract dysfunction with decreased bladder capacity and lower voiding pressure. We sought to identify which single nucleotide polymorphisms in the LOXL1 coding sequence play a role in female pelvic organ prolapse. A total of 66 patients were screened, 48 in the case group and 18 in the control group. The 7 exons of LOXL1 were evaluated for any polymorphisms. Three missense sequence changes (Arg141Leu, Gly153Asp, and Ser159Ala) and 3 silent mutations (Asp292Asp, Ala320Ala, and Ile521Ile) were identified. None of these polymorphisms were found to differ significantly in frequency in the case group compared with the control group. Our findings do not support an association of any LOXL1 exonal single nucleotide polymorphisms with the diagnosis of female pelvic organ prolapse.

Lysyl Oxidase‐Like 1 gene haplotypes and their association with pseudoexfoliation glaucoma in the Spanish population

AbstractPurpose To investigate the potential association of genetic variants across the lysyl oxidase‐like 1 (LOXL1) gene in Spanish patients with Pseudoexfoliation Glaucoma (XFG).Methods A case‐control study of 105 unrelated individuals from Spain with XFG and 200 unrelated healthy controls matched by age and ethnicity were enrolled. A region of 39,230 bp‐long of genomic DNA covering the entire LOXL1 gene and regulatory regions were sequenced in 99 patients using next generation sequencing. Variant frequencies were compared with those reported from the HapMap CEU study. Restriction fragment–length polymorphism (RFLP) analysis was conducted to genotype five SNPs in the LOXL1 gene (rs16958477, rs1048661, rs3825942, rs2165241 and rs3522) in all controls and in 6 XFG patients. A case‐control association study was performed using the HaploView 4.0 software.Results The allelic frequency analysis of the five selected LOXL1 SNPs revealed that (with the exception of rs3522) they were significantly associated with an increased risk for XFG. The haplotypes CGGT and AGGT, which carry the risk alleles of rs1048661, rs3825942, and rs2165241 were significantly associated with XFG. In contrast, the haplotypes ATGC and AGAC were found to be protective.Conclusion This study confirms that common genetic variants in the LOXL1 gene are associated with XFG in the Spanish population. To our knowledge this is the first study to demonstrate this association in a population of Western Europe.

Lack of association of LOXL1 gene variants in Japanese patients with central retinal vein occlusion without clinically detectable pseudoexfoliation material deposits.

A possible association has been reported between exfoliation syndrome (EX) and various ocular and systemic vascular disorders; however, it is unclear if there is an association between EX and central retinal vein occlusion (CRVO). Because latent deposits of exfoliation materials might not be recognized during slit-lamp examination, an ocular biopsy is required to establish a precise diagnosis. We evaluated a possible association between EX and CRVO using lysyl oxidase-like 1 (LOXL1) gene variants as alternative markers for EX. The allelic and genotypic frequencies of three LOXL1 variants (rs1048661, rs3825942, and rs2165241) were determined in 68 consecutive Japanese patients with CRVO [15 with exfoliation syndrome (EX+) and 53 without exfoliation syndrome (EX-)] and 90 control patients with cataract without EX (CT). The frequencies of the rs1048661 and rs3825942 variants showed borderline difference between the CRVO and CT groups (p = 0.04085 and p = 0.06088, respectively, for allelic frequencies, and p = 0.06838 and p = 0.03482, respectively, for genotypic frequencies). Compared with the CT group, subgroup analysis showed that the CRVO EX+ group had significant differences in the allelic and genotypic frequencies of rs1048661 (p = 0.0006447 and p = 0.0001392, respectively) and had borderline differences in the allelic and genotypic frequencies of rs3825942 (p = 0.03403 and p = 0.07341, respectively), while the CRVO EX- group did not (p = 0.1324-0.6306). Subgroup analysis showed that the frequencies of rs2165241 did not differ between the CRVO and CT groups. When the LOXL1 variants were used as disease markers for clinically undetectable EX, there was no association between CRVO and EX. The results suggested that the LOXL1 variants, which are well-established markers for EX, are not likely genetic markers for CRVO in Japanese subjects.

Lysyl oxidase-like 1 gene in the reversal of promoter risk allele in pseudoexfoliation syndrome.

This study was necessary to establish the association between common genetic variants in the lysyl oxidase-like 1 (LOXL1) gene with pseudoexfoliation (PEX) syndrome and emphasize the reversal of promoter risk allele in a South Indian population. To investigate the potential association of genetic variants across the LOXL1 gene in South Indian patients with PEX syndrome and glaucoma. A case-control study of individuals from Madurai, India, with PEX syndrome and glaucoma as well as healthy people serving as controls. Three hundred unrelated people with PEX syndrome and 225 age- and ethnically matched controls were recruited for genetic analysis. Four single-nucleotide polymorphisms in LOXL1 (rs16958477, rs1048661, rs3825942, and rs2165241) were genotyped by direct sequencing in all participants. Regulatory regions and 7 coding exons of LOXL1 were directly sequenced in 50 patients and 50 controls. A case-control association analysis was performed using the Golden Helix SVS suite. An association between 4 LOXL1 single-nucleotide polymorphisms with PEX syndrome and glaucoma was observed (rs16958477, P = 4.77 × 10-6 [odds ratio, 0.50]; rs1048661, P = 4.28 × 10-5 [1.79]; rs3825942, P = 4.68 × 10-30 [9.19]; and rs2165241, P = 1.98 × 10-15 [2.88]). Sequencing of 7 exons and regulatory regions of LOXL1 identified 11 additional sequence variants; only rs41435250 showed an association (P = 3.80 × 10-5 [0.49]) with PEX syndrome and glaucoma. Genetic variants in LOXL1 are associated with PEX syndrome and glaucoma in the South Indian population. To our knowledge, this is the first study to demonstrate the association of rs41435250 with PEX as well as reversal of the promoter risk allele. Understanding the role of the LOXL1 gene in PEX pathogenesis will facilitate early detection in individuals at risk for this condition.

Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma: a meta-analysis.

To study the associations between lysyl oxidase-like 1 (LOXL1) polymorphisms and primary open angle glaucoma (POAG) remain inconsistent. In this study, we have performed a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk. Published literature from PubMed and other databases were retrieved. All studies evaluating the association between LOXL1 polymorphisms (rs2165241, rs1048661, rs3825942) and POAG risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. Twelve studies were identified as eligible articles, with thirteen (2098 cases and 16 473 controls), thirteen (1795 cases and 2916 controls) and sixteen population cohorts (2456 cases and 2846 controls) for the association of rs2165241, rs1048661 and rs3825942 with POAG risk respectively. Overall analyses showed no association between each LOXL1 polymorphism and POAG risk, and the negative associations were remained when the subjects were stratified as Caucasian and Asian. The heterozygote of rs2165241 was associated with reduced POAG risk in hospital-based populations (TC vs CC: OR, 0.79, 95%CI: 0.63-0.99), and rs1048661 was associated with increased POAG risk in hospital-based populations in a dominant model (TT vs CC+CT: OR, 1.23, 95%CI: 1.01-1.50); however, these associations were not found in population-based subjects. This meta-analysis suggests that LOXL1 polymorphisms are not associated with POAG risk. Given the limited sample size, the associations of LOXL1 polymorphisms with POAG risk in hospital-based populations await further investigation.

Association of LOXL1 polymorphisms with pseudoexfoliation, glaucoma, intraocular pressure, and systemic diseases in a Greek population. The Thessaloniki eye study.

To investigate the association of the two single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene with pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG) in a Greek population-based setting, from the Thessaloniki Eye study. A total of 233 subjects with successful DNA extraction, PCR amplification, and genotyping were included in the genetic analysis of G153D and R141L SNPs of LOXL1 gene and classified into four groups: controls (n = 93); subjects with PEX (n = 40); POAG (n = 66); and PEXG (n = 34). Multinomial logistic regression was used to test their association with LOXL1 SNPs with adjustment for covariates. The association of LOXL1 with IOP (in untreated subjects) and with systemic diseases was explored. Both LOXL1 SNPs were present in high frequencies in controls and cases. The G153D was strongly associated with both PEX (odds ratio [OR] = 23.2, P = 0.003 for allele G) and PEXG (OR = 24.75, P = 0.003 for allele G) and was not associated with POAG (P = 0.451). In contrast, the R141L was not associated with PEX (P = 0.81), PEXG (P = 0.063), or POAG (P = 0.113). No association of the G153D with either intraocular pressure (IOP) or systemic diseases was found. In the Thessaloniki Eye Study, the G153D SNP of LOXL1 gene was strongly associated with both PEX and PEXG, whereas the R141L was not associated. No association of the LOXL1 with IOP or with systemic diseases was found. These findings further support the hypothesis that the LOXL1 gene contributes to onset of PEXG through PEX. Gene variants of LOXL1 do not help to identify those with PEX at increased risk for glaucoma development.

Correction: Association between Polymorphisms in Lysyl Oxidase-Like 1 and Susceptibility to Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Correction: Association between Polymorphisms in Lysyl Oxidase-Like 1 and Susceptibility to Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Exfoliation syndrome in sub-Saharan Africa.

The goal of this review is to estimate the burden of exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in sub-Saharan Africa and to identify the gaps in knowledge of disease prevalence in this region. PubMed, Medline, African Journals Online and Google engine search were carried out using the following terms "pseudoexfoliation" or "exfoliation syndrome Africa", "pseudoexfoliation" or "exfoliation syndrome" + "glaucoma Africa," "glaucoma prevalence Africa," "pattern of glaucoma presentation Africa," "pseudoexfoliation" or "exfoliation syndrome" + "cataract Africa," "ophthalmic conditions Africa." Studies were included if they described the proportion or prevalence/incidence of XFG and XFS in sub-Saharan Africa or if they investigated lysyl oxidase-like 1 (LOXL1) variants in XFS among Africans. 22 papers were identified and classified as clinic-based studies (n = 16) and population-based (n = 4) studies. Two other studies were considered important, and therefore, included in the review. Clinic-based studies demonstrate that XFS is a common cause of glaucoma, as is true in many other parts of the world. Furthermore, XFS often co-exists with cataract and climatic droplet keratopathy. Its prevalence ranged from 5.1 to 7.7 % in patients >40 years in population-based studies, a value that is considerably higher than that reported in African Americans. XFS was strongly associated with increasing age in the prevalence studies. The burden of XFS in sub-Saharan Africa is high. More investigation is needed to determine why clinic-based studies report virtually no XFS in some countries (Ghana and Tanzania), while nearby countries report greater proportions (Nigeria and Ethiopia).