Genetic polymorphisms of vascular endothelial growth factor and risk for retinopathy of prematurity in South of Iran

Abstract

Retinopathy of prematurity (ROP) is a multifactorial disease, that cause visual impairment in premature children. The exact pathogenesis and etiology of ROP is unknown and genetic susceptibility is considered as risk factor. Vascular endothelial growth factor (VEGF) plays a major role in retinal neovascularization and subsequently retinal detachment. VEGF polymorphism is associated with proliferative ROP in some studies. We examined the possible association of the VEGF gene polymorphisms with ROP in preterm infants in south of Iran. A total of 111 preterm infants were examined by ophthalmologist and after that were genotyped. Genotyping of the VEGF +405 (rs2010963) and VEGF +936 (rs3025039) was done by the polymerase chain reaction and restriction fragment length polymorphism methods. The frequency of VEGF alleles, genotypes and haplotype distribution were compared between groups. The patients were divided in three groups: 66 to the normal group (normal fundoscopy), and 45 to the ROP group; 30 infants were not treated with Lasertherapy (Regressive group) and 15 treated with Lasertherapy. The frequency of VEGF +405 and VEGF +936 G/C genotypes as well as allele frequencies was not different between groups. No significant difference was found between ROP with treatment and ROP without lasertherapy. Our report indicate that there is no association between the carrier states of gene polymorphisms VEGF +405, VEGF +936 and progression or spontaneous regression of ROP in preterm infants in Iranian population. However, it should be considered that angiogenesis is a complex process and genetic factors in addition to environmental factors are contributed in this pathway.

Retinopathy of prematurity: a review of risk factors and their clinical significance

“…Genetic association studies with ROP and VEGF gene have been contradictory. 15,33,87,99,142,176,197,206,222,223,305,339,343,381 The Wnt signaling pathway genes previously identified in familial exudative vitreoretinopathy, including FZD4 and LRP5 , and Norrie Disease Protein (NDP) gene have also been explored with positive associations with ROP including stage 4/5 ROP in several studies; 90,97,104,172,173,218,244,342 however, there have been only a few genetic studies with adequate sample size and refined inclusion criteria. A large genetic cohort study identified SNPs in the intronic region of brain-derived neurotrophic factor (BDNF) gene as associated with treatment-requiring ROP, which warrants further studies on functional effects of intronic variants of BDNF and replication studies.…”

Genetic Polymorphisms of Vascular Endothelial Growth Factor in Neonatal Pathologies: A Systematic Search and Narrative Synthesis of the Literature

“…In the retina of premature babies, vascularization is achieved through angiogenesis and the proliferation of endothelial cells. This proliferation occurs under the influence of VEGF, which is critical for retinal vascular development [ 92 , 93 ], and the genetic expression of VEGF has an essential role. Retinal hypoxia is associated with a marked increase in VEGF expression.…”

Association between VEGF polymorphisms (−460 T/C and +936 C/T) and retinopathy of prematurity risk: A meta-analysis

“…Single nucleotide polymorphisms (SNPs) in the VEGF −460 T/C (rs833061) and +936 C/T (rs3025039) in the respective 5′ and 3′ untranslated region (UTR) have been reported in different populations 3 . Some studies have found association of VEGF −460 T/C or +936 C/T polymorphism with ROP risk,4, 5, 6 but some other studies show no association between VEGF −460 T/C or +936 C/T polymorphism and risk of ROP 7, 8, 9, 10, 11. These studies revealed a conflicting conclusion, probably due to the relatively small size of subjects, since individual studies are usually underpowered in detecting the effect of low penetrance genes.…”