RESUMEN
Purpose. The aim of this pharmacogenetic study was to evaluate the impact of high-risk alleles in factor H, factor C3 and vascular endothelial growth factor (VEGF) on the response to intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD) in a Tunisian population. Methods. Ninety patients with active neovascular AMD treated with intravitreal bevacizumab injections were enrolled in the study. Treatment response was evaluated by comparing BCVA at baseline and at 12 months. Patients were classified into either "poor responders" (PR) or "good responders" (GR). Single nucleotide polymorphism (SNP) genotyping was performed for rs1061170 in FH, rs2230199 in C3 andrs699947, rs2010963 and rs3025039 in VEGF. The association between genotype and visual response at 12 months was assessed. Results. Seventy-seven participants were assigned to the GR group and 13 to the PR group. No correlation was found between FH, C3 and VEGF variant alleles and treatment response. However, haplotype analysis of rs699947 ((- 2578) C/A), rs2010963 ((+ 405) C/G) and rs3025039 ((+ 936) C/T) SNPs revealed that the AGT haplotype was associated with a poor response at 12months (p = 0.048). No association was found between treatment response and the cumulative effect of all high-risk alleles of C3, FH and VEGF. All three types of CNV were found in both groups at a comparable frequency. Conclusions. The VEGF haplotype TGA could be used as a marker for poor visual prognosis in Tunisian patients with neovascular AMD treated with bevacizumab.
Asunto(s)
Bevacizumab/administración & dosificación , Complemento C3/genética , Factor A de Crecimiento Endotelial Vascular/genética , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/genética , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Factor H de Complemento/genética , Femenino , Frecuencia de los Genes/genética , Humanos , Inyecciones Intravítreas , Masculino , Prevalencia , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Túnez/epidemiología , Degeneración Macular Húmeda/epidemiologíaRESUMEN
PURPOSE: To evaluate the clinical phenotype of ten Tunisian families with non-syndromic retinitis pigmentosa (RP), to characterize genes and mutations causing these conditions, and to elaborate phenotype-genotype correlations. METHODS: Descriptive clinical genetic study of 114 individuals, of whom 27 are affected by non-syndromic RP. Ophthalmic examination and various visual tests were performed. DNA was analyzed using single nucleotide polymorphism, microsatellite genotyping and direct sequencing to determine the genes and mutations involved. RESULTS: We identified seven mutated genes: RPE65, RDH12, USHER 2A, PDE6a, PDE6b, CRB1, and NR2E3. Analysis of phenotype-genotype correlation indicated that some genes were associated with specific phenotypes. In RPE65 mutations, we found early onset dystrophy, nystagmus, keratoconus, white dot deposits in earlier stages and clumped pigment in later stages. The RDH12-associated phenotype (juvenile RP) showed severe and early-onset dystrophy, diffuse spicule pigmentation, macular edema and thickening, and tomographic re-organization of retinal layers. The CRB1 mutation was characterized by preserved para-arteriolar retinal pigment epithelium and no hemeralopia. CONCLUSION: RP is clinically and genetically heterogeneous. The two ultimate goals of research are to provide efficient clinical diagnostic of affected gene by phenotype-genotype correlation and to design novel treatment regimens. Our goal is to create a specific chip for our population, and then future research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina and the development of gene therapy approaches.
Asunto(s)
Estudios de Asociación Genética , Retinitis Pigmentosa/genética , Adolescente , Adulto , Niño , Estudios de Cohortes , Análisis Mutacional de ADN , Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo de Nucleótido Simple , Túnez , Adulto JovenRESUMEN
To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. The frequency of the CFH 402H allele was significantly higher in AMD patients than in controls (p = 2.62 × 10(-16)). However, subgroup analysis does not reveal any association between the variant allele H and phenotypes of AMD or CNV. Also, there was no significant difference in response to bevacizumab treatment according to Y402H CFH genotype (p = 0.59). A strong association of the 402H allele with susceptibility to AMD in the Tunisian population was confirmed; however, this variant does not appear to be involved in the clinical progression of this disease or in the postintravitreal bevacizumab response.
Asunto(s)
Degeneración Macular/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab , Estudios de Casos y Controles , Factor H de Complemento/genética , Femenino , Angiografía con Fluoresceína , Frecuencia de los Genes , Genotipo , Humanos , Inyecciones Intravítreas , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Túnez , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiologíaRESUMEN
In this cross-sectional study, we evaluated H. pylori seroprevalence and the relevant factors in 1518 people aged > or = 6 years from the general population of Nahavand, western Islamic Republic of Iran. Questionnaires covering sociodemographic variables were completed by interview. Blood samples were taken from each individual. Sera were tested for anti-H. pylori IgG using commercial enzyme immunoassay. Overall, seroprevalence of H. pylori was high, 71.0% (95% CI: 69.0%-73.0%). There was a gradual increase with age. Based on multivariate adjustment, only female sex and age could be considered risk factors.
Asunto(s)
Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Adolescente , Adulto , Distribución por Edad , Anciano , Anticuerpos Antibacterianos/sangre , Distribución de Chi-Cuadrado , Niño , Estudios Transversales , Femenino , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Humanos , Inmunoglobulina G/sangre , Irán/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Vigilancia de la Población , Factores de Riesgo , Estudios Seroepidemiológicos , Distribución por Sexo , Factores Socioeconómicos , Adulto JovenRESUMEN
To investigate a possible association between functional polymorphisms of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22-R620W) and receptors for the Fc fragment of IgG (FcgRIIa-H131R, FcgRIIIa-F158V FcgRIIIb-NA1/NA2), and rheumatoid arthritis (RA), 133 Tunisian patients with RA and 100 controls were genotyped. We found strong evidence of an association of PTPN22 620W allele and RA. However, analysis does not detect an association between auto-antibodies seropositivity, presence of nodules or erosions and this allele. No significant skewing of any of the three FcgR polymorphisms was seen in this RA group. Nevertheless, we identified FcgRIIIa-V/V158 as the most important FcgR genotype for severe disease subset with joint erosions and observed that patients with FcgRIIIb-NA2/NA2 genotype had an earlier incidence of clinical symptoms. In conclusion, we have confirmed that PTPN22 620W allele is associated with Tunisian RA but does not constitute a factor influencing clinical manifestations. Conversely, this study supports that the FcgRIIa/IIIa and IIIb polymorphisms could influence the course and the severity of this disease. A large number of samples are required to provide independent confirmation of these findings.
Asunto(s)
Artritis Reumatoide/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Receptores de IgG/genética , Adulto , Anciano , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Artritis Reumatoide/sangre , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Genotipo , Antígenos HLA-DR/genética , Antígenos HLA-DR/inmunología , Cadenas HLA-DRB1 , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factor Reumatoide/sangre , Factor Reumatoide/inmunología , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , TúnezRESUMEN
In this cross-sectional study, we evaluated H. pylori seroprevalence and the relevant factors in 1518 people aged > /= 6 years from the general population of Nahavand, western Islamic Republic of Iran. Questionnaires covering sociodemographic variables were completed by interview. Blood samples were taken from each individual. Sera were tested for anti-H. pylori IgG using commercial enzyme immunoassay. Overall, seroprevalence of H. pylori was high, 71.0% [95% CI: 69.0%-73.0%]. There was a gradual increase with age. Based on multivariate adjustment, only female sex and age could be considered risk factors