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1.
Artigo em Inglês | MEDLINE | ID: mdl-34299682

RESUMO

The Mayan population of Guatemala is understudied within eye and vision research. Studying an observational homogenous, geographically isolated population of individuals seeking eye care may identify unique clinical, demographic, environmental and genetic risk factors for blinding eye disease that can inform targeted and effective screening strategies to achieve better and improved health care distribution. This study served to: (a) identify the ocular health needs within this population; and (b) identify any possible modifiable risk factors contributing to disease pathophysiology within this population. We conducted a cross-sectional study with 126 participants. Each participant completed a comprehensive eye examination, provided a blood sample for genetic analysis, and received a structured core baseline interview for a standardized epidemiological questionnaire at the Salama Lions Club Eye Hospital in Salama, Guatemala. Interpreters were available for translation to the patients' native dialect, to assist participants during their visit. We performed a genome-wide association study for ocular disease association on the blood samples using Illumina's HumanOmni2.5-8 chip to examine single nucleotide polymorphism SNPs in this population. After implementing quality control measures, we performed adjusted logistic regression analysis to determine which genetic and epidemiological factors were associated with eye disease. We found that the most prevalent eye conditions were cataracts (54.8%) followed by pseudoexfoliation syndrome (PXF) (24.6%). The population with both conditions was 22.2%. In our epidemiological analysis, we found that eye disease was significantly associated with advanced age. Cataracts were significantly more common among those living in the 10 districts with the least resources. Furthermore, having cataracts was associated with a greater likelihood of PXF after adjusting for both age and sex. In our genetic analysis, the SNP most nominally significantly associated with PXF lay within the gene KSR2 (p < 1 × 10-5). Several SNPs were associated with cataracts at genome-wide significance after adjusting for covariates (p < 5 × 10-8). About seventy five percent of the 33 cataract-associated SNPs lie within 13 genes, with the majority of genes having only one significant SNP (5 × 10-8). Using bioinformatic tools including PhenGenI, the Ensembl genome browser and literature review, these SNPs and genes have not previously been associated with PXF or cataracts, separately or in combination. This study can aid in understanding the prevalence of eye conditions in this population to better help inform public health planning and the delivery of quality, accessible, and relevant health and preventative care within Salama, Guatemala.


Assuntos
Catarata , Síndrome de Exfoliação , Catarata/etnologia , Catarata/genética , Estudos Transversais , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/genética , Estudo de Associação Genômica Ampla , Guatemala/epidemiologia , Humanos , Indígenas Centro-Americanos
2.
PLoS One ; 16(4): e0250772, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909695

RESUMO

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the gene encoding LOXL1 are risk factors for exfoliation syndrome and exfoliation glaucoma. This meta-analysis comprehensively investigated the association between LOXL1 gene polymorphisms (rs1048661, rs3825942, and rs2165241) and the risk of exfoliation syndrome/exfoliation glaucoma (XFS)/(XFG). METHODS: All eligible case-control studies, published before August 17, 2020, were searched on Medline (Ovid), PubMed, CNKI, EMBASE, and Wanfang databases. RESULTS: In total, 5022 cases and 8962 controls were included in this meta-analysis. Significant associations between LOXL1 gene polymorphisms and XFS/XFG risk was observed in the disease types-based subgroups. In addition, in the subgroup analysis of ethnicity, positive associations between LOXL1 gene polymorphisms (rs1048661, rs3825942, and rs2165241) and XFS/XFG risk were found in Caucasians. Furthermore, rs1048661 and rs3825942 polymorphisms were related to XFS/ XFG risk in Asians; however, no significant association was observed between the LOXL1 gene rs2165241 polymorphism and XFS/XFG risk in Asians. In addition, rs1048661 and rs3825942 correlated with XFS/XFG susceptibility in Africans. CONCLUSIONS: Our results implicate LOXL1 gene polymorphisms as XFS/XFG risk factors, especially in Caucasians.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Polimorfismo de Nucleotídeo Único , População Negra/genética , Estudos de Casos e Controles , Síndrome de Exfoliação/etnologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , População Branca/genética
3.
Genes (Basel) ; 12(1)2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396423

RESUMO

Glaucoma, the world's leading cause of irreversible blindness, is a complex disease, with differential presentation as well as ethnic and geographic disparities. The multifactorial nature of glaucoma complicates the study of genetics and genetic involvement in the disease process. This review synthesizes the current literature on glaucoma and genetics, as stratified by glaucoma subtype and ethnicity. Primary open-angle glaucoma (POAG) is the most common cause of glaucoma worldwide, with the only treatable risk factor (RF) being the reduction of intraocular pressure (IOP). Genes associated with elevated IOP or POAG risk include: ABCA1, AFAP1, ARHGEF12, ATXN2, CAV1, CDKN2B-AS1, FOXC1, GAS7, GMDS, SIX1/SIX6, TMCO1, and TXNRD2. However, there are variations in RF and genetic factors based on ethnic and geographic differences; it is clear that unified molecular pathways accounting for POAG pathogenesis remain uncertain, although inflammation and senescence likely play an important role. There are similar ethnic and geographic complexities in primary angle closure glaucoma (PACG), but several genes have been associated with this disorder, including MMP9, HGF, HSP70, MFRP, and eNOS. In exfoliation glaucoma (XFG), genes implicated include LOXL1, CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A. Despite tremendous progress, major gaps remain in resolving the genetic architecture for the various glaucoma subtypes across ancestries. Large scale carefully designed studies are required to advance understanding of genetic loci as RF in glaucoma pathophysiology and to improve diagnosis and treatment options.


Assuntos
Síndrome de Exfoliação/genética , Proteínas do Olho/genética , Predisposição Genética para Doença , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Aberto/genética , Proteínas do Tecido Nervoso/genética , Adulto , Idoso , Povo Asiático , População Negra , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/patologia , Feminino , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Fechado/etnologia , Glaucoma de Ângulo Fechado/patologia , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/patologia , Hispânico ou Latino , Humanos , Pressão Intraocular , Masculino , Herança Multifatorial , Polimorfismo Genético , Fatores de Risco , População Branca
4.
Invest Ophthalmol Vis Sci ; 60(1): 134-146, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30629727

RESUMO

Purpose: Glaucoma, a leading cause of blindness worldwide, often remains undetected until irreversible vision loss has occurred. Treatments focus on lowering intraocular pressure (IOP), the only modifiable and readily measurable risk factor. However, IOP can vary and does not always predict disease progression. MicroRNAs (miRNAs) are promising biomarkers. They are abundant and stable in biological fluids, including plasma and aqueous humor (AqH). We aimed to identify differentially expressed miRNAs in AqH and plasma from glaucoma, exfoliation syndrome (XFS), and control subjects. Methods: Plasma and AqH from two ethnic cohorts were harvested from glaucoma or XFS (often associated with glaucoma, n = 33) and control (n = 31) patients undergoing elective surgery. A custom miRNA array measured 372 miRNAs. Molecular target prediction and pathway analysis were performed with Ingenuity Pathway Analysis (IPA) and DIANA bioinformatical tools. Results: Levels of miRNAs in plasma, a readily accessible biomarker source, correlated with miRNA levels in AqH. Twenty circulating miRNAs were at least 1.5-fold higher in glaucoma or XFS patients than in controls across two ethnic cohorts: miR-4667-5p (P = 4.1 × 10-5), miR-99b-3p (P = 4.8 × 10-5), miR-637 (P = 5.1 × 10-5), miR-4490 (P = 5.7 × 10-5), miR-1253 (P = 6.0 × 10-5), miR-3190-3p (P = 3.1 × 10-4), miR-3173-3p (P = 0.001), miR-608 (P = 0.001), miR-4725-3p (P = 0.002), miR-4448 (P = 0.002), and miR-323b-5p (P = 0.002), miR-4538 (P = 0.003), miR-3913-3p (P = 0.003), miR-3159 (P = 0.003), miR-4663 (P = 0.003), miR-4767 (P = 0.003), miR-4724-5p (P = 0.003), miR-1306-5p (P = 0.003), miR-181b-3p (P = 0.004), and miR-433-3p (P = 0.004). miR-637, miR-1306-5p, and miR-3159, in combination, allowed discrimination between glaucoma patients and control subjects (AUC = 0.91 ± 0.008, sensitivity 85.0%, specificity 87.5%). Conclusions: These results identify specific miRNAs as potential biomarkers and provide insight into the molecular processes underlying glaucoma.


Assuntos
Humor Aquoso/metabolismo , Biomarcadores/sangue , Síndrome de Exfoliação/sangue , Glaucoma de Ângulo Aberto/sangue , MicroRNAs/sangue , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/cirurgia , Feminino , Perfilação da Expressão Gênica , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Estados Unidos/epidemiologia , População Branca/etnologia
6.
Nat Genet ; 49(7): 993-1004, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28553957

RESUMO

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Estudo de Associação Genômica Ampla , Mutação de Sentido Incorreto , Mutação Puntual , Idoso de 80 Anos ou mais , Alelos , Aminoácido Oxirredutases/fisiologia , Substituição de Aminoácidos , Povo Asiático/genética , Canais de Cálcio/genética , Adesão Celular , Síndrome de Exfoliação/etnologia , Matriz Extracelular/metabolismo , Olho/metabolismo , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Chaperonas Moleculares/biossíntese , Chaperonas Moleculares/genética , RNA Mensageiro/biossíntese , Esferoides Celulares
7.
J Glaucoma ; 25(1): 62-94, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25304275

RESUMO

AIM: There were several studies that have researched the associations between lysyl oxidase-like 1 (LOXL1) gene polymorphism and the susceptibility to exfoliation syndrome (XFS)/exfoliation glaucoma (XFG), but results have been inconclusive. MATERIALS AND METHODS: A meta-analysis was performed for deriving more exact estimation of the relationship. Twenty-five studies were selected for studying rs1048661 and rs3825942. Sixteen studies were selected for studying rs2165241. RESULTS: Single nucleotide polymorphism (SNP) rs1048661 was found to be associated with XFS/XFG, but the risk allele in white populations was found to be G, as opposite to the T allele in Japanese, Chinese, and Korean populations. The SNP rs3825942 was significantly associated with XFS in this black South African population. However, the AA genotype of rs3825942 confers XFS risk in this population, as opposed to the GG genotype described in all other populations. SNP rs2165241 was found to be associated with XFS/XFG, but the risk allele in white populations was found to be T, as opposite to the "C" allele in Japanese and Korean populations. CONCLUSIONS: Our meta-analysis indicates that rs1048661 ("G" alleles) had weak association with XFG/XFS; rs3825942 ("G" alleles) had strongly association with XFG/XFS; and rs2165241("T" alleles) had significant risk with XFG/XFS in some ethnicity.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Alelos , Etnicidade , Síndrome de Exfoliação/etnologia , Genótipo , Glaucoma de Ângulo Aberto/etnologia , Haplótipos , Humanos , Pressão Intraocular , Pessoa de Meia-Idade
8.
Invest Ophthalmol Vis Sci ; 56(10): 5838-43, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26348632

RESUMO

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Aminoácido Oxirredutases/metabolismo , Catarata/metabolismo , Metilação de DNA , Síndrome de Exfoliação/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aminoácido Oxirredutases/genética , Estudos de Casos e Controles , Catarata/etnologia , Catarata/genética , China/etnologia , Ilhas de CpG/genética , Etnicidade , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo
9.
Ann Hum Genet ; 79(6): 431-50, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26404116

RESUMO

Pseudoexfoliation (PEX) is an age-related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic-based meta-analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06-0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02-0.06) and Koreans (OR = 0.10, 95%CI:0.05-0.22). These associations we-re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22-17.41) and Koreans (OR = 6.63, 95%CI:2.60-16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/genética , Predisposição Genética para Doença , Alelos , Povo Asiático/genética , População Negra/genética , Intervalos de Confiança , Etnicidade/genética , Genótipo , Haplótipos , Humanos , Modelos Estatísticos , Razão de Chances , Polimorfismo de Nucleotídeo Único , População Branca/genética
11.
Curr Eye Res ; 40(12): 1218-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25849827

RESUMO

PURPOSE: The aim of this study was to explore the potential association of genetic variants across clusterin (CLU) and tumor necrosis factor-alpha (TNF-α) genes in South Indian individuals with pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG). MATERIALS AND METHODS: A total of 523 individuals including 299 unrelated cases (150 PEXS and 149 PEXG) and 224 age- and ethnically-matched healthy controls were recruited for genetic analysis. Six single-nucleotide polymorphisms (SNPs) including, five CLU SNPs (rs11136000, rs2279590, rs9331888, rs9331931, rs3087554) and one promoter SNP (rs1800629) of TNF-α were genotyped in all study subjects. Genotyping of CLU SNPs were performed using the TaqMan allelic discrimination assay while TNF-α SNP was genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis. Association analysis was performed by determining the distributions of genotype and allele frequencies, Hardy-Weinberg equilibrium, and chi-square p values and odds ratios as implemented in the Golden Helix SNP & Variation Suite (SVS). RESULTS: Five CLU SNPs did not show any significant differences in allele frequencies between patients and control subjects (rs3087554, p = 0.919, OR = 1.01, 95% CI: 0.77-1.33; rs2279590, p = 0.432, OR = 1.12, 95% CI: 0.84-1.51; rs9331931, p = 0.310, OR = 1.24, 95% CI: 0.81-1.89; rs11136000, p = 0.072, OR = 1.31, 95% CI: 0.97-1.76; rs9331888, p = 0.911, OR = 1.01, 95% CI: 0.78-1.31). The investigation of TNF-α SNP established a significant association with PEXS and PEXG (p = 0.042, OR = 0.61, 95% CI: 0.38-0.99). However, this association did not remain significant after Bonferroni correction. CONCLUSIONS: Our data suggest that genetic variants in CLU and TNF-α genes do not play a major role in the development of PEXS and PEXG in the South Indian population.


Assuntos
Clusterina/genética , Síndrome de Exfoliação/genética , Glaucoma/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Idoso , Idoso de 80 Anos ou mais , Síndrome de Exfoliação/etnologia , Feminino , Frequência do Gene , Técnicas de Genotipagem , Glaucoma/etnologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , População Branca/etnologia
12.
Acta Ophthalmol ; 93(4): 362-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25270165

RESUMO

PURPOSE: To study the safety and long-term efficacy of classic viscocanalostomy in patients with open-angle glaucoma (OAG) in different populations. METHODS: A total of 726 eyes of 726 patients from Europe or South Africa with primary OAG (POAG) and pseudoexfoliative glaucoma (PXFG) were included in this retrospective multicentre study. Complete (qualified) success was defined as an intraocular pressure (IOP) equal to or lower than 21, 18 and 16 mmHg without (with or without) medications, respectively. A failed procedure was defined if IOP was above 21 mmHg, not controllable by laser goniopuncture or medications. RESULTS: The mean IOP before surgery was 42.6 ± 14.2 mmHg for all patients, 29.6 ± 6.6 mmHg for European patients and 48.1 ± 12.9 mmHg for African patients. The follow-up time was 86.2 ± 43.1 months. Mean IOP was 15.4 ± 3.6 mmHg at 5 years, 15.5 ± 4.4 mmHg at 10 years and 16.8 ± 4.2 mmHg at 15 years. The qualified success rate for an IOP of 21, 18 or 16 mmHg or less after 5 years was 92% [95% confidence interval (CI) 0.88-0.96], 70% (95% CI 0.63-0.77) and 43% (95% CI 0.36-0.51) in European patients, and 90% (95% CI 0.87-0.93), 77% (95% CI 0.74-0.81) and 67% (95% CI 0.63-0.72) in African patients, respectively. There was no difference between the success rate for POAG and PXFG for an IOP of 21, 18 or 16 mmHg or less at 5 years (p = 0.64, p = 0.20, p = 0.22, respectively). Laser goniopuncture was performed postoperatively on a total of 127 eyes (17.7%), lowering the pressure from 23.1 ± 1.9 mmHg to 15.0 ± 2.2 mmHg. There were no significant complications, in particular, no blebitis or endophthalmitis. CONCLUSION: Viscocanalostomy produced a sustained long-term reduction of IOP with a low-risk profile in European and African patients with OAG over 12 years.


Assuntos
Cirurgia Filtrante/métodos , Glaucoma de Ângulo Aberto/cirurgia , Limbo da Córnea/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/fisiopatologia , Síndrome de Exfoliação/cirurgia , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Ácido Hialurônico/uso terapêutico , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tonometria Ocular , Viscossuplementos/uso terapêutico , Acuidade Visual/fisiologia , População Branca , Adulto Jovem
13.
Invest Ophthalmol Vis Sci ; 55(7): 4238-43, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24917141

RESUMO

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Aminoácido Oxirredutases/genética , DNA/genética , Síndrome de Exfoliação/genética , Glaucoma de Ângulo Aberto/genética , Pressão Intraocular , Polimorfismo Genético , Vigilância da População , Idoso , Alelos , Aminoácido Oxirredutases/metabolismo , Estudos Transversais , Etnicidade/genética , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/metabolismo , Grécia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Fatores de Risco , Tonometria Ocular , População Urbana
14.
Sci Rep ; 4: 5340, 2014 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-24938310

RESUMO

The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). However, the risk allele of a variant in LOXL1 has been found to be inverted between Asian and Caucasian populations. Therefore, we newly performed a genome-wide association study using 201 XFS/XFG and 697 controls in Japanese, and identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs) distributing in not only LOXL1 but also TBC1D21 and PML at the 15q24.1 locus. These SNPs were confirmed by an independent population consisted of 121 XFS/XFG and 263 controls in Japanese. Moreover, further analyses revealed a unique haplotype structure only from the combination of TBC1D21 and LOXL1 variants showing a high XFS/XFG susceptibility specific for the Asian population. Although there still should be other gene(s) in the other region(s) contributing to the disease process, these results suggested that the combination of newly discovered variants in these genes might be useful for precise XFG risk assessment, as well as for elucidating the molecular mechanism of XFG pathogenesis through XFS.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Proteínas Ativadoras de GTPase/genética , Predisposição Genética para Doença/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Síndrome de Exfoliação/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Japão , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteína da Leucemia Promielocítica , Fatores de Risco , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética
15.
Zhonghua Yan Ke Za Zhi ; 50(2): 126-32, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24735667

RESUMO

OBJECTIVE: In this study, we evaluate the association profiles of the lysyl oxidase-like 1 ( LOXL1) gene polymorphisms with exfoliation syndrome in XFS Uygur population. METHODS: Case-control study. Sixty-four unrelated Uygur patients with XFS (including 7 patients with Exfoliation Syndrome Glaucoma) and 127 Uygur control subjects were included. All of control subjects were selected from the same area, passed through the same ophthalmic checks and confirmed without any expressions of XFS. Most of them suffered from cataract and other ophthalmic disease.Genotypes of the three single nucleotide polymorphisms (SNPs) of LOXL1 (rs1048661, rs2165241 and rs3825942) were analyzed by direct sequencing following PCR amplification, and a case-control association study was performed and judged by odd ratio (OR) with (95% confidential interval). RESULTS: G allele of rs1048661 [OR:1.92 (1.14-3.22)], G of rs3825942 [OR:4.86 (2.02-11.68)], and T of rs2165241[OR:3.98 (2.54-6.25)] were risk alleles for the disorder. The genotypes TT for rs2165241 [OR:2.20 (1.04-4.65)] were risk genotypes for the disease. CONCLUSION: LOXL1 is a susceptibility gene of XFS in the Uygur populations. The risk alleles of rs1048661, rs3825942 and rs2165241 in Uygur subjects were identified to be significantly associated with XFS individually.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Etnicidade/genética , Síndrome de Exfoliação/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
16.
PLoS One ; 9(3): e90331, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24603551

RESUMO

The present knowledge on the association of single nucleotide polymorphisms (SNPs) of lysyl oxidase-like 1 (LOXL1) with pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG) is controversial and inconclusive. This meta-analysis sought to derive a more precise estimation of the effects of LOXL1 SNP loci (rs1048661, rs3825942, and rs2165241) on PEXS/PEXG. Literature searches were conducted on the PubMed, EMBASE, ISI Web of Science, and Cochrane Library databases through October 2013. Twelve studies describing 1810 cases and 1790 controls met the inclusion criteria. The strengths of the associations found through the meta-analysis were assessed with pooled odds ratios and their 95% confidence intervals (CI). A meta-regression analysis was also used to examine the influence of the study and population characteristics. The results indicated that rs1048661 TT carriers had 92.1% and 40.4% less risk of developing PEXS/PEXG than did the controls in the Caucasian and Asian populations, respectively. Carriers of rs3825942 AA or rs2165241 CC also had significantly less PEXS/PEXG susceptibility than did the non-carriers. Meta-regression showed that in Caucasians, the male proportion (slope: 0.272; 95% CI: 0.167-0.376; P = 0.0001) and mean age (slope: 0.796; 95% CI: 0.375-1.217; P = 0.0002) of the PEXS/PEXG subjects correlated positively with the effect of rs3825942 on PEXS/PEXG susceptibility. The meta-analysis suggested that LOXL1 rs1048661 TT, rs3825942 AA, and rs2165241 CC were associated with a reduced risk of developing PEXS/PEXG.


Assuntos
Aminoácido Oxirredutases/genética , Síndrome de Exfoliação/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Fatores Etários , Idoso , Alelos , Povo Asiático/genética , Síndrome de Exfoliação/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fatores Sexuais , População Branca/genética
17.
J Glaucoma ; 22(2): 110-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23358209

RESUMO

BACKGROUND: Until population-based data become available in Ethiopia, hospital-based studies may reflect the distribution of the subtypes of glaucoma in certain parts of the country. PURPOSE: The main aim of this study was to determine the subtypes of glaucoma in Jimma University Hospital, Ethiopia. METHODS: A facility-based cross-sectional study was conducted in Jimma University Hospital from April 1, 2007 to March 30, 2008. The study population consisted of 335 consecutive new and follow-up patients with glaucoma diagnosed based on strict objective criteria. RESULTS: The mean (SD) age of the study patients was 57.0 (12.7) years (range, 8 to 90 y). The male to female ratio was 2.7:1. The 2 most common subtypes of glaucoma found were exfoliation glaucoma (35.2%) and primary open angle glaucoma (32.8%). Primary angle closure glaucoma was diagnosed in 18.5% of patients. CONCLUSIONS: The finding of exfoliation glaucoma as the most common subtype of glaucoma in the present clinic-based study is interesting. Such observation has never been reported from anywhere in Africa. We recommend community-based surveys to define the real distribution of the glaucoma subtypes in Ethiopia.


Assuntos
População Negra , Síndrome de Exfoliação/etnologia , Glaucoma de Ângulo Fechado/etnologia , Glaucoma de Ângulo Aberto/etnologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos Transversais , Etiópia/epidemiologia , Feminino , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Distribuição por Sexo , Acuidade Visual/fisiologia , Adulto Jovem
18.
Curr Eye Res ; 38(3): 358-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23186005

RESUMO

PURPOSE: To study the possible mechanism and treatment for pigment dispersion glaucoma (PDG) caused by single-piece acrylic (SPA) intraocular lens (IOL) ciliary sulcus fixation in Asian eyes. MATERIALS AND METHODS: Patients referred for PDG caused by SPA IOL ciliary sulcus fixation to our hospital from April 2005 to June 2011 were included. The patients' general information, IOL type, interval between initial surgery and PDG occurrence, examination findings, antiglaucoma medicine regimen and surgical interventions were recorded. RESULTS: In total, six eyes from five Chinese patients were included in this study. The intraocular pressure (IOP) increased 19-30 days after cataract surgery and was not satisfactorily controlled with antiglaucoma medication. Dense pigmentation was deposited on the IOLs and on the anterior chamber angle. IOL haptic chafing was noted on the rear iris surface. IOL repositioning in the capsular bag was performed in three eyes and was combined with trabeculectomy in two eyes with progressive glaucoma. An IOL exchange with three-piece IOL ciliary sulcus fixation was performed in the other three eyes. Scanning electron microscopy of the explanted IOLs demonstrated a rough edge on the IOL haptics. CONCLUSIONS: SPA IOLs were not suitable for ciliary sulcus fixation. The chafing effect of the IOL haptics on the posterior iris pigment epithelium could induce PDG in Asian eyes. IOLs should be positioned in the capsular bag or a three-piece IOL should be used instead.


Assuntos
Extração de Catarata , Corpo Ciliar/lesões , Síndrome de Exfoliação/etiologia , Traumatismos Oculares/etiologia , Lentes Intraoculares/efeitos adversos , Epitélio Pigmentado Ocular/patologia , Resinas Acrílicas , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Povo Asiático , Corpo Ciliar/cirurgia , Remoção de Dispositivo , Síndrome de Exfoliação/etnologia , Síndrome de Exfoliação/terapia , Traumatismos Oculares/etnologia , Traumatismos Oculares/terapia , Feminino , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trabeculectomia , Acuidade Visual/fisiologia , Adulto Jovem
20.
Clin Exp Ophthalmol ; 40(5): 454-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21902787

RESUMO

BACKGROUND: Pseudoexfoliation syndrome (XFS) has been found to occur more commonly among indigenous Australians. This paper was designed to determine the prevalence of XFS within the indigenous Australian population living in central Australia. DESIGN: Clinic-based cross-sectional study. PARTICIPANTS: One thousand eight hundred eighty-four individuals living in one of 30 remote communities within the statistical local area of 'Central Australia' were recruited. This equated to 36% of those aged 20 years or older and 67% of those aged 40 years or older within this district. METHODS: Participants aged 20 years or over were recruited as they presented to the eye clinic at each remote community. Slit-lamp examination was performed, and the presence of XFS in each eye was recorded and presented. MAIN OUTCOME MEASURE: Prevalence and associations of XFS. RESULTS: XFS was present in one or both eyes of 4.7% of the individuals recruited into the study. Prevalence increased with age (5.9% of those ≥40 years and 12.7% ≥ 60 years). There was a significant association between the presence of XFS and climatic keratopathy (χ(2) = 240.13; P < 0.00001). Notably, none of those with XFS had ocular hypertension or glaucoma. CONCLUSION: XFS was present in a significantly higher proportion of indigenous Australians compared with previously reported prevalence estimates among non-indigenous Australians. The association found between XFS and climatic keratopathy may represent a common causal link between the two conditions. The lack of association of XFS with ocular hypertension and glaucoma appears to be a unique feature of the indigenous Australian population, and this merits further investigation.


Assuntos
Síndrome de Exfoliação/etnologia , Glaucoma/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/etnologia , População Rural/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Northern Territory/epidemiologia , Prevalência , Distribuição por Sexo , Adulto Jovem
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