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Vascular endothelial growth factor genetic polymorphisms and susceptibility to age-related macular degeneration in Tunisian population.

ABSTRACT: PURPOSE:Three VEGF SNPs (-2578) C/A, (+405) G/C and (+936) C/T were investigated in Tunisian exudative AMD patients in order to determine their association with the disease susceptibility and their influence to intravitreal bevacizumab therapy response. METHODS:145 AMD patients and 207 age-matched controls were included. 68 patients were treated with intravitreal bevacizumab. SNPs genotyping were performed using direct sequencing. The serum VEGF was assayed by ELISA (R&D). RESULTS:The (+405) CC and (+936) TT genotypes were higher in AMD patients than in controls (p?=?5?×?10(-6) and p?=?0.021, respectively). The mean plasma levels of VEGF were statistically higher in AMD patients (84.22 pg/ml) than in controls (15 pg/ml). Three months after bevacizumab treatment, 52 patients (85.6%) were classified as good responders (GR) and 16 (14.4%) as poor responders (PR). The mean plasmatic-VEGF levels in GR patients was higher (86.61?±?80.30 pg/ml) than in PR patients (47.12?±?45.74 pg/ml) (p?=?0.086). The patients with genotype homozygous TT (+936) would be PR compared to those carrying CT and CC genotypes. Whereas, those with AA (-2578) genotype would be GR compared with others genotypes (p?=?0.014; p?=?0.042 respectively). CONCLUSIONS:Our results show that VEGF genetic variants may contribute to the susceptibility to neovascular AMD in Tunisian patients.

SUBMITTER: Habibi I

PROVIDER: S-EPMC4145361 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Vascular endothelial growth factor genetic polymorphisms and susceptibility to age-related macular degeneration in Tunisian population.

Habibi Imen I Sfar Imen I Chebil Ahmed A Kort Fedra F Bouraoui Rim R Jendoubi-Ayed Salwa S Makhlouf Mouna M Abdallah Taïeb Ben TB El Matri Leila L Gorgi Yousr Y

Biomarker research 20140818

<h4>Purpose</h4>Three VEGF SNPs (-2578) C/A, (+405) G/C and (+936) C/T were investigated in Tunisian exudative AMD patients in order to determine their association with the disease susceptibility and their influence to intravitreal bevacizumab therapy response.<h4>Methods</h4>145 AMD patients and 207 age-matched controls were included. 68 patients were treated with intravitreal bevacizumab. SNPs genotyping were performed using direct sequencing. The serum VEGF was assayed by ELISA (R&D).<h4>Resu ...[more]

PMID: 25165559

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Project description:PurposeA previously published study demonstrated a pharmacogenetic association between the minor alleles of 2 VEGFR2 single nucleotide polymorphisms (SNPs) and greater improvement in visual acuity (VA) to treatment with ranibizumab, an anti-vascular endothelial growth factor (VEGF) drug, in patients with neovascular age-related macular degeneration (AMD). We evaluated whether this association was replicated among patients who participated in the Comparison of AMD Treatments Trials (CATT) or the Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) trial.DesignCohort studies within randomized clinical trials.ParticipantsEight hundred thirty-five patients participating in CATT and 512 patients participating in IVAN.MethodsEach patient was genotyped for the SNPs rs4576072 and rs6828477 in the VEGFR2 gene.Main outcomes measuresMean change in VA from baseline to 1 year after initiation of treatment with ranibizumab or bevacizumab. Differences in VA response between the patient group homozygous for the minor allele of each SNP and the other genotype groups were evaluated with analysis of variance. Differences in VA response by the number of minor alleles present for either SNP or both combined were evaluated with tests of linear trend. Analyses were conducted separately for CATT and IVAN participants and with both the studies combined.ResultsNo statistically significant difference in mean change in VA was identified between genotypes of either SNP (P ≥ 0.05). Furthermore, a stepwise analysis failed to show a significant interaction for either SNP based on the number of minor alleles present. The lack of association was similar in both the CATT and IVAN cohorts and whether the analysis combined patients treated with either ranibizumab or bevacizumab or when restricted to patients treated with ranibizumab only.ConclusionsThe CATT and IVAN data do not support a pharmacogenetic association between the 2 VEGFR2 SNPs, rs4576072 and rs6828477, and change in VA in response to anti-VEGF therapy in patients with neovascular AMD.

Project description:BACKGROUND:Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older. OBJECTIVES:The objective of this review was to investigate the effects of anti-VEGF (vascular endothelial growth factor) modalities for treating neovascular AMD. SEARCH STRATEGY:We searched CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006, 2007 for ongoing trials. SELECTION CRITERIA:We included randomized controlled trials (RCTs). DATA COLLECTION AND ANALYSIS:Two review authors independently extracted data. We contacted trial authors for additional data. We summarized outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean differences. MAIN RESULTS:We included five RCTs of good methodological quality. All five trials were conducted by pharmaceutical companies. An intention-to-treat analysis using the last observation carried forward method was done in most trials. Two trials compared pegaptanib versus sham. One trial compared ranibizumab versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin PDT versus verteporfin PDT alone. Fewer patients treated with pegaptanib lost 15 or more letters of visual acuity at one year follow-up compared to sham (pooled relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for 1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13 (95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for 0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and 3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60). The NNT was 4.35 (95% CI 2.78 to 11.11). Pooled RR for gain of 15 or more letters visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab plus verteporfin PDT versus verteporfin PDT. Frequency of endophthalmitis in included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with pegaptanib. Improvement in vision-specific quality of life was reported for both treatments. AUTHORS' CONCLUSIONS:Pegaptanib and ranibizumab reduce the risk of visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in visual acuity in many eyes. Quality of life and cost will be important for treatment decisions. Other agents blocking VEGF are being tested in ongoing trials.

Project description:PurposeTo describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).DesignCohort study.ParticipantsPatients enrolled in the Comparison of AMD Treatments Trials.MethodsPatients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At 5 years, patients were recalled for examination.Main outcome measuresVisual acuity (VA) and morphologic retinal features.ResultsVisual acuity was obtained for 647 of 914 (71%) living patients with average follow-up of 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most patients (60%) were treated 1 time or more with a drug other than their assigned drug. At the 5-year visit, 50% of eyes had VA of 20/40 or better and 20% had VA of 20/200 or worse. Mean change in VA was -3 letters from baseline and -11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm(2), a mean of 4.8 mm(2) larger than at 2 years. Geographic atrophy was present in 213 of 515 (41%) gradable eyes and was subfoveal in 85 eyes (17%). Among 555 eyes with spectral-domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% sub-retinal pigment epithelium). Mean foveal total thickness was 278 μm, a decrease of 182 μm from baseline and 20 μm from 2 years. The retina was abnormally thin (<120 μm) in 36% of eyes. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (-4 letters; P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups.ConclusionsVision gains during the first 2 years were not maintained at 5 years. However, 50% of eyes had VA of 20/40 or better, confirming anti-vascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD.

Dataset Information

Vascular endothelial growth factor genetic polymorphisms and susceptibility to age-related macular degeneration in Tunisian population.

Publications

Vascular endothelial growth factor genetic polymorphisms and susceptibility to age-related macular degeneration in Tunisian population.

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