Research Information System
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey
Approval Date: 2013
Student: BURÇİN KEPEZ YILDIZ
Supervisor: ŞENGÜL ÖZDEK
Abstract:The prevalance of advanced age diseases has been increased by increasing mean survival age in human populations. Age related Macula Degeneration (AMD) which is advanced age disease is the most important blindness cause in people aged over 50 in developed countries. AMD is a disease charecterized by chronic and progressive degeneration of photoreceptors, the underlying retinal pigment epithelium (RPE), Bruch?s membrane and, possibly, the choriocapillaris in the macula. The patogenesis of disease involves a number of enviromental and genetic factors. Recently it has been established that single nucleotide polymorphism rs1061170 on chromosome 1q 32 leads variation in coding and this variation is strongly asoociated with age related macular degeneration. There are limited studies investigating the association between genetic variations and age related macular degeneration in Turkish population. The aim of this study is to evaluate genetic polymorphisms in complement factor H and VEGF genes and their relationship with intravitreal anti VEGF treatment responses. For this purpose 109 patients and 70 healthy controls were included. 109 patients were seperated into two groups as `responders? and `nonresponders? based on the change at clinical activity score after three dosages of intravitreal anti VEGF per month . Genetic analysis revealed that VEGF rs 2146323 and VEGF rs699947 single nucleotide polymorphisms were similarly distributed between control and patient groups so these polymorphisms were determined to be unrelated with age related macular degeneration. When we reviewed both patient and control groups for complement factor H Y402H polymorphism, in patient group there were 42 patients (%38,5) and in control group only 11 healthy controls (%15,7) had homozygot wild genotype TT. Additionally variant C allel frequency was %45 in in controls and %31,7 in patient group. (p:0,011) These results make us consider that Y402H polymorphism might be protective for age related macular degeneration rather than a risk factor. Median plasma levels of interleukin-6 which was analysed to evaluate genotype-phenotype relation were detected to be similar between patient and control groups;( control: 18,07 pg/ml, patients: 22,08 pg/ml, p: 0,594 ) but different between responders and non-responders. The median plasma level was 27,3 pg/ml in responders and significantly higher than nonresponders (nonresponders: 9,8 pg/ml; p<0,001). Additionally the patients with homozygot wild genotype were detected to have higher plasma levels of interleukin 6 than heterozygotes and homozygot variants. (p: 0,013) When we examined complement factor H and VEGF rs 2146323 , rs699947 single nucleotid polymorphisms in patient group together with clinical parameters like gain in best corrected visual acuity, changes in central foveal thickness on OCT, decrease in pigment epitelyum detachment height, regression in lesion dimensions, number of injections and follow up time ; we have only found a relationship that we have given no clinical emphasis between rs 699947 AC genotype and regression in lesion dimensions and that AC genotype tended to have more regression in lesion area than homozygot normals(AA) . There was no difference between other genotypes and all other clinical parameters. This study is the first study in Turkish population that searches the association between VEGF rs2146323,rs699947 single nucleotide polymorphisms and age related macular degeneration and also the association between VEGF, complement factor H polymorphisms and response to the intravitreal anti VEGF treatment. We consider that further studies are necessary to investigate the association between genetic variants and age related macular degeneration.