ABSTRACT
Neovascular age-related macular degeneration (nAMD) is a progressive ocular disease, responsible for central visual loss and blindness in elderly population. Increase data demonstrate that genetic factors play an important role in pathogenesis process of this disease. The aim of this study is to investigate the association between rs3732378 polymorphism in CX3CR1 gene and nAMD in a sample of Algerian patients. This case-control study consisted of 72 patients with nAMD and 124 control subjects. DNA of participants was extracted using salting out method. Genotyping was carried out using the TaqMan real-time polymerase chain reaction method. Statistical analysis was performed by SPSS.21.0. The prevalence of the risk genotype AA was higher in the nAMD group than in control group (OR=5.02, 95% CI=1.44-17.4, P=0.011). In our sample of Algerian patients, the rs3732378 polymorphism is associated with nAMD. This result may support the role of CX3CR1 gene in the pathogenesis of nAMD.
ABSTRACT
Background: Increasing evidence shows that genetic and environmental factors can influence neovascular age-related macular degeneration (nAMD) risk. The aim of this study was first to analyse the association of insertion/deletion polymorphism in VEGF gene and environmental factors with the risk of nAMD, and then to investigate whether these factors have an impact on the age of onset of nAMD in a sample of the Algerian population. Methods: Seventy two patients with nAMD and one hundred twenty-four controls were recruited; standardized questionnaire was used to collect information regarding underlying systemic diseases and important environmental factors. Genotyping of VEGF (I/D) SNP was conducted using PCR-based assay approach, and statistical analyses were conducted using IBM SPSS statistics 21. Results: A significant association was reported of age (p < 0.05), smoking (p = 0.02), alcohol (p < 0.01), hypertension (p = 0.04), hyperlipidaemia (p = 0.008) and thyroid disease (p = 0.03) with nAMD. Also, Thyroid disease may have a role in accelerating the development of nAMD in an earlier age in our sample (p < 0.001). No association was found between the VEGF 2549 I/D genotype and the presence of nAMD (p = 0.27), neither with the age of onset of nAMD (p = 0.21). Conclusion: Our results suggest that age, smoking, alcohol, hypertension, hyperlipidaemia and thyroid diseases are possible risk factors that could increase the risk of nAMD in a sample of Algerian population. In addition, VEGF 2549 I/D might not be associated with the risk of nAMD development. Finally, thyroid disease may accelerate the development of nAMD in an earlier age.
Introduction: Un nombre croissant de preuves montrent que les facteurs génétiques et environnementaux peuvent influencer le risque de la forme néovasculaire de la dégénérescence maculaire liée à l'âge (DMLAn). L'objectif de cette étude était d'abord d'analyser l'association du polymorphisme d'insertion/délétion dans le gène VEGF et des facteurs environnementaux avec le risque de la DMLAn, puis d'étudier si ces facteurs ont un impact sur l'âge d'apparition de cette maladie dans un échantillon de population algérienne. Méthodes: Soixante-douze patients atteints de la DMLA et 124 témoins ont été recrutés ; un questionnaire standardisé a été utilisé pour recueillir des informations concernant les maladies systémiques sous-jacentes et les facteurs environnementaux importants. Le génotypage du SNP VEGF (I/D) a été réalisé par une l'approche de PCR standard, et les analyses statistiques ont été réalisées à l'aide du logiciel IBM SPSS statistics 21. Résultats: Une association significative a été rapportée entre l'âge (p < 0,05), le tabagisme (p = 0,02), l'alcool (p < 0,01), l'hypertension (p = 0,04), l'hyperlipidémie (p = 0,008) et les maladies thyroïdiennes (p = 0,03) avec la DMLAn. Les maladies thyroïdiennes peuvent jouer un rôle dans l'accélération du développement de la DMLAn à un âge plus précoce dans notre échantillon (p < 0,001). Aucune association n'a été trouvée entre le génotype VEGF 2549 I/D et la présence de la DMLA néovasculaire (p = 0,27), ni avec l'âge d'apparition de cette pathologie (p = 0,21). Conclusion: Nos résultats suggèrent que l'âge, le tabagisme, l'alcool, l'hypertension, l'hyperlipidémie et les maladies thyroïdiennes sont des facteurs de risque possibles qui pourraient augmenter le risque de la DMLA néovasculaire. De plus, le VEGF 2549 I/D pourrait ne pas être associé au risque de développement de la DMLA. Enfin, les maladies thyroïdiennes pourraient accélérer le développement de la DMLAn à un âge plus précoce.
Subject(s)
Hypertension , Macular Degeneration , Humans , Vascular Endothelial Growth Factor A/genetics , Algeria/epidemiology , Vascular Endothelial Growth Factors , Polymorphism, Genetic , Ethanol , Macular Degeneration/etiology , Macular Degeneration/geneticsABSTRACT
PURPOSE: The aim of this case-control study was to determine the impact of environmental factors on the predisposition to develop keratoconus in a sample of Western Algerian population. Subsequently, we were interested in the implication of two single nucleotide polymorphisms (SNPs) IL4 rs2070874 and FOXP3 rs3761548, previously described as contributing to the occurrence of allergy, in the development of keratoconus. METHODS: The study included 70 unrelated KC cases and 70 controls originating from Western Algeria. DNA genotyping was done using predesigned probe-based allelic discrimination TaqManâ assays. Allele and genotype frequencies were compared between the cases and controls by Chi-square test and odds ratios with 95% confidence intervals. RESULTS: A significant association between risk factors such as family history, atopy, eye rubbing, and the development of keratoconus was found in our sample. Smoking would provide a protective effect against the pathology. No statistically significant differences were found in the allele and genotype frequencies between cases and controls neither for IL4 rs2070874 nor for FOXP3 rs3761548. CONCLUSION: Our study provides, for the first time, a clear demonstration of the absence of association of the allergy-associated IL4 and FOXP3 polymorphisms with KC in a sample from Western Algerian population.
ABSTRACT
The aim of this study was to detect the genetic alterations in the Factor 8 gene in 26 patients from Western Algeria. We detected the presence of "intron 22 inversion" with long-range polymerase chain reaction (PCR). Negative patients for this inversion were analyzed for "intron 1 inversion" using multiplex PCR. Patients who were negative for both inversions were analyzed using a direct sequencing. Deleterious effects of novel mutations on protein were assayed with bioinformatics tools. Causing mutations were identified in 85.71% of the families, including 11 "intron 22 inversion," 1 "intron 1 inversion," and 6 different point mutations (2 nonsense, 1 splice site, and 3 missense mutations). Among these mutations, c.2189G > A (p.Cys711Tyr) and c.5219+1G>T are novel. This is the first study that reports spectrum of mutations in the Factor 8 gene in the Western Algerian population. Knowledge of these mutations is important for genetic counseling and medical care of affected families.
