Genetic Variants of Interleukin 17A Are Functionally Associated with Increased Risk of Age-Related Macular Degeneration

Inflammation ◽  
2014 ◽  
Vol 38 (2) ◽  
pp. 658-663 ◽  
Author(s):  
Shaoru Zhang ◽  
Yonghua Liu ◽  
Shilin Lu ◽  
Xinmeng Cai
Keyword(s):  
Macular Degeneration ◽  
Genetic Variants ◽  
Age Related Macular Degeneration ◽  
Interleukin 17A ◽  
Age Related ◽  
Increased Risk

Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

2021 ◽  
pp. 112067212110026
Author(s):  
Pablo Gili ◽  
Leyre Lloreda Martín ◽  
José-Carlos Martín-Rodrigo ◽  
Naon Kim-Yeon ◽  
Laura Modamio-Gardeta ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Gene Polymorphisms ◽  
Age Related Macular Degeneration ◽  
Spanish Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

scholarly journals Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Maria Grazia Mazzone ◽  
Francesco Giuliano ◽  
Antonella Agodi
Keyword(s):  
Public Health ◽  
Personalized Medicine ◽  
Macular Degeneration ◽  
Complement System ◽  
Genetic Variants ◽  
Age Related Macular Degeneration ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Age Related ◽  
Gene Environment

Age-related macular degeneration (AMD) is the most common cause of visual loss in developed countries, with a significant economic and social burden on public health. Although genome-wide and gene-candidate studies have been enabled to identify genetic variants in the complement system associated with AMD pathogenesis, the effect of gene-environment interaction is still under debate. In this review we provide an overview of the role of complement system and its genetic variants in AMD, summarizing the consequences of the interaction between genetic and environmental risk factors on AMD onset, progression, and therapeutic response. Finally, we discuss the perspectives of current evidence in the field of genomics driven personalized medicine and public health.

Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: two population cohorts

2021 ◽  
Author(s):  
Liv Tybjærg Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Ruth Frikke-Schmidt ◽  
Børge Grønne Nordestgaard
Keyword(s):  
Macular Degeneration ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Age Related ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Plasma Apolipoprotein

Abstract Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.

Relationship between Aflibercept Efficacy and Genetic Variants of Genes Associated with Neovascular Age-Related Macular Degeneration: The BIOIMAGE Trial

2020 ◽  
Vol 243 (6) ◽  
pp. 461-470
Author(s):  
Anniken Burés Jelstrup ◽  
Esther Pomares ◽  
Rafael Navarro ◽  
Keyword(s):  
Macular Degeneration ◽  
Genetic Variants ◽  
Treatment Efficacy ◽  
Retinal Pigment ◽  
Predictive Biomarkers ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Extension Phase ◽  
Open Label ◽  
Age Related

<b><i>Purpose:</i></b> To identify the genetic variants of the vascular endothelial growth factor (VEGF) pathway genes and other genes associated with neovascular age-related macular degeneration (nAMD) as possible predictive biomarkers of a favorable treatment response to aflibercept. <b><i>Design:</i></b> A 52-week (with extension phase: 104-week), prospective, open-label, single-arm, multicenter, phase IV trial was conducted in Spain. <b><i>Participants:</i></b> Patients with nAMD were enrolled. <b><i>Methods:</i></b> Aflibercept was administered every 8 weeks until week 48 (after 1-monthly loading doses over 3 months). After week 48, the interval between visits for aflibercept administration was extended by 2 weeks per visit to a maximum of 12 weeks if no evidence of disease activity was observed. A total of 338 SNPs in 90 genes associated with nAMD were analyzed. <b><i>Main Outcome Measures:</i></b> Efficacy was evaluated mainly with best-corrected visual acuity (BCVA), and adverse events (AEs) were reported. Treatment efficacy was defined as an increase in BCVA ≥15 letters versus the baseline visit. Univariate and multivariate logistic regressions were used to associate single-nucleotide polymorphisms (SNPs) and treatment efficacy. <b><i>Results:</i></b> 194 nonconsecutive patients were enrolled, 170 completed the 52-week follow-up, and of the 85 patients who started the extension phase, 77 completed this phase. Mean BCVA increased from baseline to weeks 52 and 104 by 9 and 10 letters (<i>p</i> = 0.0001 for both), respectively. The percentages of patients gaining ≥15 letters in weeks 52 and 104 were 33 and 31%, respectively. Multivariate logistic regression showed significant associations of 6 SNPs (in 6 genes) with treatment efficacy: rs12366035 (<i>VEGFB</i>; TT; odds ratio [OR] 217), rs25681 (<i>C5</i>; AA/AG; OR 19.7/8.3), rs17793056 (<i>CX3CR1</i>; CT/CC; OR 8.1/6.2), rs1800775 (<i>CETP</i>; CC; OR 6.6), rs2069845 (<i>IL6</i>; GG/AA; OR 5.6/3.3), and rs13900 (<i>CCL2</i>; CT; OR 4.0). One percent of the patients reported arteriothrombolic events related to aflibercept (cerebrovascular accident) according to the Antiplatelet Trialist Collaboration, and 2% reported serious ocular (retinal pigment epithelial tear, retinal tear, and endophthalmitis) and systemic (cardiac failure, hypersensitivity, and transient ischemic attack) AEs related to aflibercept. <b><i>Conclusions:</i></b> Results suggest strong pharmacogenetic associations between one genetic variant of <i>VEGFB</i> (TT, rs12366035) and<i> C5</i> (AA, rs12366035) genes and the BCVA response after 52-week aflibercept treatment in patients with nAMD. Likewise, the results support the efficacy of aflibercept observed in phase III studies and a good safety profile.

scholarly journals Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration

2020 ◽  
Vol 12 ◽  
pp. 251584142090392
Author(s):  
Constantinos D. Georgakopoulos ◽  
Olga E. Makri ◽  
Athina Pallikari ◽  
Konstantinos Kagkelaris ◽  
Panagiotis Plotas ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Blood Coagulation ◽  
Intravitreal Injection ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Clinical Effects ◽  
Coagulation Parameters ◽  
Age Related ◽  
Increased Risk ◽  
Treatment Naïve

Purpose: Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. Methods: Treatment-naïve patients with age-related macular degeneration ( n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. Results: The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. Conclusion: A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. ClinicalTrials.gov ID: NCT03509623.

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