Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Ragkousis Antonios
Dissertation committee:
Ειρήνη Χατζηράλλη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παναγιώτης Θεοδοσιάδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ηλίας Γεωργάλας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παρασκευή Μουτσάτσου-Λαδικού, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Δρούτσας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πέτρος Πέτρου, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χρήστος Κρούπης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Γενετική μελέτη ασθενών με απόφραξη φλέβας αμφιβληστροειδούς
Translated title:
Genetic analysis in patients with retinal vein occlusion
Summary:
Purpose:
Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Another purpose of this study was to determine whether these specific genetic polymorphisms affect the response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with macular oedema secondary to retinal vein occlusion (RVO).
Methods:
Participants in this case-control study were 50 RVO patients with macular oedema secondary to RVO (RVO group) and 50 healthy volunteers (control group). The patients were treated with intravitreal ranibizumab or aflibercept and were followed-up for 12 months after initiation of treatment. Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
Results:
The dominant genetic model of the association analysis for the PON1 Q192R single nucleotide polymorphism (SNP) revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. With reference to treatment response, patients with the LL genotype of the PON1 L55M SNP had statistically significantly higher reduction in central subfield thickness (CST) at month 12 after initiation of intravitreal anti-VEGF treatment (101.63 ± 56.80 μm in LL vs. 72.44 ± 39.41 μm in LM vs. 40.25 ± 19.33 μm in MM, p = 0.026). Patients with the M allele of the PON1 L55M SNP were statistically significantly associated with lower reduction in CST compared to non-carriers (68.29 ± 38.77 μm in LM + MM vs. 101.63 ± 56.80 μm in LL, p = 0.032).
Conclusions:
These findings suggest that the R allele of the PON1 Q192R SNP is likely to play a role as a risk factor for retinal vein occlusion. The novel finding of this study is that the presence of M allele of PON1 L55M SNP was associated with significantly lower reduction in CST after intravitreal anti-VEGF treatment in patients with macular oedema due to RVO, suggesting that PON1 L55M SNP may serve as a promising genetic biomarker for predicting response to intravitreal anti-VEGF treatment in patients with macular oedema due to RVO.
Main subject category:
Health Sciences
Keywords:
Retinal vein occlusion, Genetic polymorphisms, Paraoxonase 1, Apolipoprotein E, Stromal cell-derived factor 1
Number of references:
169
