ABSTRACT
Background: Involvement of genetic factors like gene polymorphisms was found to contribute significantly to development and progression of Primary Open Angle Glaucoma [POAG] in the last few decades
Aim of study: The present study was carried out to investigate association of PPAR-y [rs 0865710] and CYP46A1 [rs754203] gene polymorphism with development of POAG in hypertensive North Indians
Patients and methods: Study included 328 individuals, 226 as POAG cases and 102 controls. PPAR-y and CYP46A1 gene polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]
The genotypic and allelic frequency distribution in patients and controls was analyzed by SPSS [version 12.0]
Results: In CYP46A1 gene polymorphism, TT genotype and T allele were found to be associated with a significantly decreased risk of POAG whereas the CT, CC genotypes and C allele were associated with an increased risk of POAG in both hypertensive and normotensive individuals. In PPAR-y gene polymorphism, only GG genotype was nearly associated with POAG in only hypertensive cases
Conclusions: CYP46A1 [rs754203] gene polymorphism was associated with POAG in both hypertensive and normotensive patients whereas, only GG genotype of PPAR-y [rs!0865710] SNP shows significant association with POAG in hypertensive POAG patients
Subject(s)
Humans , Female , Male , Adult , Middle Aged , Glaucoma, Open-Angle/genetics , PPAR gamma , Cholesterol 24-Hydroxylase , Polymorphism, Restriction Fragment Length , Polymerase Chain Reaction , GenotypeABSTRACT
OBJETIVO: O glaucoma primário de ângulo aberto é uma doença degenerativa do nervo óptico que se encontra entre as principais causas de cegueira no mundo. Aspectos familiares já foram implicados como fatores importantes e comprovados em inúmeros estudos. Nesse artigo, apresentamos uma revisão sistemática dos trabalhos sobre glaucoma primário de ângulo aberto e DNA mitocondrial e fazemos uma análise estatística à luz dos conceitos da cienciometria. MÉTODOS: A pesquisa bibliográfica de trabalhos envolvendo DNA mitocondrial e glaucoma primário de ângulo aberto foi realizada por meio da base de dados do sítio Scopus. Foi feito o levantamento a partir das palavras-chaves "Mitochondrial DNA" e "Glaucoma" em todos os campos para publicações no período compreendido de 1992 até agosto de 2012. Finalmente, foi realizada a estatística e cienciometria com os principais dados: autores que publicaram sobre o assunto DNA mitocondrial e glaucoma; revistas e outras publicações que tiveram trabalhos relacionados com o tema; Centros de Pesquisa e Universidades que mais publicaram e países onde foram realizados os estudos sobre DNA mitocondrial e glaucoma. RESULTADOS: Identificamos que esses estudos têm aumentado sobremaneira ao longo dos últimos anos, mas ainda se encontram confinados, na maior parte, a alguns centros de pesquisa e concentrados em seletos grupos de autores na área da oftalmologia em países desenvolvidos. No Brasil, ainda não temos pesquisas publicadas sobre o assunto até o momento. CONCLUSÃO: Esses estudos são de fundamental importância para a elucidação das causas genéticas do glaucoma e para o desenvolvimento de novas terapias que não visem tão somente a diminuição da pressão intraocular.
OBJECTIVE: Primary open angle glaucoma is a neurodegenerative disease of the optic nerve that represents one of the main causes of blindness worldwide. Familial aspects have been implicated in the development of the disease and proved in several studies. In this article, we present a systematic review of works about primary open angle glaucoma and mitochondrial DNA and a statistic analyses under a scientometric insight. METHODS: Bibliographic research of the works on mitochondrial DNA and primary open angle glaucoma was made accessing the site Scopus. Then, search with the keywords "mitochondrial DNA" and "glaucoma" in all fields for publications between 1992 and august of 2012 was performed. Finally, we did the statistics and scientometric analyses with the main data, such as: authors who published articles on mitochondrial DNA and glaucoma; journals that had publications about the issue; Centers of Research, Universities and countries where most of the studies on glaucoma and mitochondrial DNA were made. RESULTS: We identified that these articles have increased in the last few years, though yet confined, mostly, to some centers of research and concentrated in selected groups of researchers in ophthalmology of developed countries. In Brazil, we do not have any article published about the issue, yet. CONCLUSION: These studies are extremely important to the elucidation of the genetic causes of glaucoma and for the development of new therapies aiming not only the reduction of the intraocular pressure.
Subject(s)
Bibliometrics , DNA, Mitochondrial , Glaucoma, Open-Angle/genetics , Intraocular Pressure , Scientific and Technical Publications , Databases, Bibliographic , Evaluation Studies as TopicABSTRACT
Glaucoma is a major cause of blindness worldwide. A single nucleotide polymorphism of the MTHFR gene [C677T] has been associated with susceptibility to this disease, although this is controversial in the last decade. In this study, the possible association between the MTHFR C677T polymorphism and the risk of developing primary open angle [POAG] and pseudoexfoliation glaucoma [PEXG] was investigated. For this, a prospective study consisting of 73 POAG, 85 PEXG and 90 matched controls was undertaken in an Iranian population. Genomic DNA was extracted from whole blood. Genotyping of all individuals for the MTHFR C677T polymorphism was conducted using the PCR-RFLP technique. Our findings revealed no significant association between the MTHFR C677T polymorphism in POAG and PEXG compared with controls. Consistent with several other studies, our analysis suggests that the MTHFR C677T polymorphism is unlikely to be a factor contributing to the risk of developing specific forms of glaucoma
Subject(s)
Humans , Female , Male , Middle Aged , Aged , Exfoliation Syndrome , Glaucoma, Open-Angle/genetics , Polymorphism, Restriction Fragment Length , Case-Control Studies , Genotyping Techniques , Polymorphism, Single Nucleotide , Prospective Studies , Methylenetetrahydrofolate Reductase (NADPH2)ABSTRACT
PURPOSE: To verify if patients with primary open-angle glaucoma with HLA class I haplotypes (A9-B12, A2-B40, A1-B8) associated with this disease may have a greater rate of progression than patients who do not present these haplotypes. METHODS: Anatomical and functional glaucoma evaluation (cup-to-disc ratio and visual field) of 25 patients (six of them with one of the haplotypes associated with glaucoma) followed at the Glaucoma Outpatient Clinic of the University Hospital, Ribeirão Preto School of Medicine, São Paulo University (HCFMRP-USP) for ten years after typing of their HLA antigens in order to compare with their previous condition. RESULTS: A greater increase of the cup-to-disc ratio was observed in patients with HLA haplotypes associated with primary open-angle glaucoma predisposition. However, no significant differences in functional damage progression or in retinal nerve fibers loss were detected between them and other patients with glaucoma. CONCLUSION: The present results indicate an association of class I HLA haplotypes with progression of anatomic alterations of the optic nerve head in glaucomatous patients.
OBJETIVO: Verificar se pacientes com glaucoma primário de ângulo aberto portadores de haplotipos HLA de classe I (HLA - A9-B12; -A2-B40; e -A1-B8) associados a essa doença poderiam ter progressão maior do que pacientes que não apresentassem esses haplotipos. Método: Avaliação anatômica e funcional de 25 pacientes (6 dos quais com um dos haplotipos associados a glaucoma), seguidos no Ambulatório de Glaucoma do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), por dez anos depois da tipificação de seus antígenos HLA, para comparação com as condições anteriores. RESULTADOS: Houve aumento maior da relação escavação/disco em pacientes com haplotipos HLA associados com predisposição para glaucoma primário de ângulo aberto, no entanto não foram encontradas diferenças significantes entre esses e outros pacientes com glaucoma na progressão do dano fisiológico e nem na perda de fibras nervosas da retina. CONCLUSÃO: Os resultados indicam a associação de haplotipos HLA de classe I com maior taxa de progressão das alterações anatômicas da cabeça nervo óptico em pacientes com glaucoma.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Glaucoma, Open-Angle/genetics , HLA Antigens/genetics , Haplotypes/genetics , Age Factors , Alleles , Disease Progression , Glaucoma, Open-Angle/physiopathology , Optic Nerve/anatomy & histology , Time Factors , Visual Fields/physiologyABSTRACT
Glaucomas comprise a group of hereditary optic neuropathies characterized by progressive and irreversible visual field loss and damage to the optic nerve head. It is a complex disease with multiple molecular mechanisms underlying its pathogenesis. Genetic heterogeneity is the hallmark of all glaucomas and multiple chromosomal loci have been linked to the disease, but only a few genes have been characterized, viz. myocilin (MYOC), optineurin (OPTN), WDR36 and neurotrophin-4 (NTF4) in primary open angle glaucoma (POAG) and CYP1B1 and LTBP2 in congenital and developmental glaucomas. Case-control-based association studies on candidate genes involved in different stages of glaucoma pathophysiology have indicated a very limited involvement. The complex mechanisms leading to glaucoma pathogenesis indicate that it could be attributed to multiple genes with varying magnitudes of effect. In this review, we provide an appraisal of the various efforts in unraveling the molecular mystery in glaucoma and also some future directions based on the available scientific knowledge and technological developments.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Autoantibodies/immunology , Cell Death , Chromosome Mapping , Complement System Proteins/immunology , Cytochrome P-450 Enzyme System/genetics , Cytoskeletal Proteins/genetics , Epistasis, Genetic , Eye Proteins/genetics , Gene Expression , Genetic Heterogeneity , Genome, Human , Glaucoma/genetics , Glaucoma/immunology , Glaucoma/physiopathology , Glaucoma, Open-Angle/genetics , Glycoproteins/genetics , Humans , Nerve Growth Factors/genetics , Ocular Hypertension/etiology , Retinal Ganglion Cells , Risk Factors , Transcription Factor TFIIIA/geneticsABSTRACT
OBJECTIVE: The aim of this study was to determine the prevalence of open angle glaucoma in first-degree relatives accompanying POAG patients during routine examination in a reference hospital. METHOD: First-degree relatives of primary open angle glaucoma patients who accompanied their relatives to the glaucoma service of a reference hospital were screened for glaucoma. RESULTS: One-hundred and one first-degree relatives were examined, of which 56.4 percent had never had their intraocular pressure measured. 10.9 percent had previously been diagnosed with glaucoma, and 5.9 percent were newly diagnosed during this study. CONCLUSIONS: The eye examination of first-degree relatives identified a significant percentage of individuals with glaucoma. Despite being first-degree relatives of glaucoma patients, 56.4 percent of the companions had never had their eye pressure measured, demonstrating a lack of awareness about this disease.
Subject(s)
Female , Humans , Male , Middle Aged , Family Health , Glaucoma, Open-Angle/epidemiology , Nuclear Family , Brazil/epidemiology , Genetic Predisposition to Disease , Glaucoma, Open-Angle/genetics , Intraocular Pressure , Mass Screening , Prevalence , Prospective Studies , Risk FactorsABSTRACT
OBJETIVO: Identificar nos representantes de famílias com glaucoma primário de ângulo aberto (GPAA) mutações no exon 3 do gene TIGR/MYOC e avaliar a expressão fenotípica associada às mutações encontradas em seus respectivos núcleos familiares. MÉTODOS: Setenta e oito pacientes (81,2%), com pelo menos um representante na família com GPAA, e dezoito pacientes (18,7%) com glaucoma esporádico tiveram o exon 3, do gene TIGR/MYOC, submetido a seqüenciamento automático para identificação de mutações. Os pacientes, com mutação não silenciosa identificadas nesta triagem inicial, tiveram os heredogramas de suas famílias construídos. Todos os seus familiares disponíveis foram submetidos a exame oftalmológico e seqüenciamento automático do exon 3, do gene TIGR/MYOC.RESULTADOS: Foram identificados quatro tipos de variações na seqüência do exon 3 do TIGR/MYOC (Cys433Arg, Pro370Pro, Lys398Arg e Tyr347Tyr) nos 96 pacientes inicialmente estudados. A mutação Lys398Arg previamente descrita como polimorfismo não segregou com a doença na família estudada. A mutação Cys433Arg foi a mais prevalente afetando 3,1% da amostra inicial (3/96). Em duas diferentes famílias (56 integrantes disponíveis para exame), 8/56 carregavam a mutação Cys433Arg e tinham GPAA, 5/56 com mutação eram hipertensos oculares e 8/56 com mutação não apresentavam manifestações da doença. Pacientes com GPAA apresentaram mediana de idade de diagnóstico de 43,25 anos, variando entre 17-58, e média de pressão intra-ocular (PIO) de 36,3±3,8 mmHg para olho direito e 37,6±9,75 mmHg para olho esquerdo. O grupo com a mutação Cys433Arg apresentou PIO significantemente mais elevada (p<0,0007) e relação escavação/disco vertical mais comprometida (p<0,023) que o grupo de pacientes sem mutação.CONCLUSÃO: A mutação no exon 3 do gene TIGR/MYOC associa-se com famílias brasileiras portadoras de GPAA de início precoce. O fenótipo desta mutação é caracterizado por variável idade de diagnóstico, causando GPAA-juvenil e GPAA do adulto, PIO bastante elevada, de difícil controle, freqüentemente levando a grave comprometimento visual.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged, 80 and over , Exons/genetics , Eye Proteins/genetics , Glaucoma, Open-Angle/genetics , Glycoproteins/genetics , Mutation/genetics , Phenotype , DNA Mutational Analysis , Genotype , Polymerase Chain ReactionABSTRACT
La contribución de la genética molecular al estudio de enfermedades hereditarias es innegable. Existen numerosos reportes de genes responsables de enfermedades hereditarios que facilitan al diagnóstico, pronóstico y también la posibilidad de terapias cuando se conoce el defecto molecular involucrado. Además, hay cientos de enfermedades en donde la identificación del defecto molecular está cerca porque se han localizado regiones cromosómicas específicas en donde se sabe, residen genes responsables de estas enfermedades. Una estrategia es precisamente, refinar paulatinamente esta ubicación a fin de caracterizar el defecto molecular, todo ello con miras a establecer posibles tratamientos. El glaucoma primario de ángulo abierto (GPAA) es una enfermedad hereditaria que puede llevar a la ceguera si no hay un diagnóstico temprano y tratamiento. Hasta ahora, se conocen seis genes que son responsables de la enfermedad y nuestro grupo está trabajando en la caracterización genético-molecular de GPAA en familias peruana usando marcadores microsatélites a fin de caracterizar su asociación con los seis grupos de marcadores. Reportamos el hallazgo de una familia peruana afectada con GPAA que no segrega con ninguno de los marcadores microsatélites de las diferentes regiones cromosómicas que se sabe están asociadas con la enfermedad. Esto apunto a la existencia de un nuevo locus responsable del GPAA en esta familia.
Molecular genetic studies are increasingly important for the study of heredity diseases and its contribution is well known. There are several hundred reports of genes responsible of genetic diseases that help in diagnosis, prognosis and possible treatment when the molecular defect is known. Primary open-angle glaucoma (POAG) is a hereditary disease that can lead to blindness if untreated. There are six known loci that can cause it and or group is working on the characterization of Peruvian families using microsatellite markers located on regions known to harbor glaucoma genes. We found a Peruvian family that does not segregate with any of the markers located near known glaucoma loci. This would account for a new locus responsible for the disease in this family.
Subject(s)
Humans , Glaucoma, Open-Angle , Glaucoma, Open-Angle/genetics , Pathology, Molecular , Microsatellite Repeats , Family , PeruABSTRACT
Primary open angle glaucoma (POAG) is the most common form of glaucoma and the second leading cause of blindness in the world. Discovery of the candidate gene MYOC (TIGR/MYOC) encoding the protein myocilin, believed to have a role in cytoskeletal function, might play a key role in understanding the pathogenesis of POAG. MYOC is expressed in many ocular tissues, including trabecular meshwork (TM), a specialised eye tissue essential in regulating intraocular pressure (IOP). Later it was shown to be the trabecular meshwork inducible-glucocorticoid response protein (TIGR). Mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma (JOAG). The unprocessed myocilin with signal peptide is a 55-kDa protein with 504 amino acids. Mature myocilin is known to form multimers. Wild type myocilin protein is normally secreted into the trabecular extracellular matrix (ECM) and there appears to interact with various ECM materials. It is believed that the deposition of high amounts of myocilin in trabecular ECM could affect aqueous outflow either by physical barrier and/or through cell-mediated process leading to elevation of IOP. The N-terminal region of the myocilin has sequence similarity to myosin (muscle protein) and the C-terminal of the protein has an olfactomedin-like domain. Structural and genetic studies of the MYOC gene and its protein product along with molecular modeling could lead to better understanding of the pathogenesis of POAG. This review highlights the current understanding of myocilin and the relevance of genetic and structural work.
Subject(s)
Cytoskeletal Proteins/chemistry , Eye Proteins/chemistry , Glaucoma, Open-Angle/genetics , Glycoproteins/chemistry , Humans , Molecular Structure , Trabecular Meshwork/metabolismABSTRACT
Se revisan los aspectos relacionados con la influencia genética en el desarrollo del glaucoma primario de ángulo abierto. El patrón exacto de herencia en el glaucoma primario de ángulo abierto no está establecido y es probablemente debido a la presencia de varios tipos de herencia los cuales son modificados por otros factores genéticos y ambientales. No está claro en qué momento se debe solo a la herencia o cuando esta se encuentra asociada a otros factores
Subject(s)
Humans , Eye Diseases, Hereditary , Glaucoma, Open-Angle/genetics , Risk FactorsABSTRACT
Se presentaron los resultados de un estudio realizado en 72 pacientes con glaucoma primario de ángulo abierto y sus familiares. Las familias se agruparon según patrón de herencia y se relacionó el tipo de herencia con antecedentes patológicos personales, edad y sexo. Se obtuvo el 50 porciento de familias con patrón de herencia no definido, el 25 por5ciento con patrón autosómico dominante y el 25 porciento con patrón autosómico recesivo
Subject(s)
Humans , Glaucoma, Open-Angle/genetics , Cross-Sectional Studies , Epidemiologic StudiesABSTRACT
Se presenta una pareja de gemelos monocigóticas, con un seguimiento clínico de 10 años portadoras de un síndrome exfoliativo, con una expresión no concordante por lo que se sospecha la influencia de factores ambientales, sobre una base genética