Association of Previously Verified Gene Polymorphisms With AMD in Turkish Population (AMD-SNP)

August 29, 2016 updated by: Umit Ubeyt INAN, Kocatepe University

A Multicenter Study on the Investigation of Previously Verified Leading Gene Polymorphisms Related to Age-related Macular Degeneration in Turkish Population

The purpose of this study is to determine whether common genetic polymorphisms that have been verified to be related to age-related macular degeneration (AMD) in some populations are also associated with AMD in Turkish population

Study Overview

Status

Unknown

Conditions

Detailed Description

Age-related macular degeneration (AMD) remains as the most important cause of severe visual impairment of elderly people in developed countries. It is one of the best-characterized complex trait diseases. Multiple genetic and environmental factors play a role in the pathogenesis. A number of different biological pathways and related gene polymorphisms are strongly implicated in its etiology. A lot of chromosomal locations have been studied to figure out genetic risk factors responsible from the development of AMD. Most genetic variants that have been found to be related to AMD at least in one study have not been verified in subsequent studies. However in recent years, single-nucleotide polymorphisms related to the complement system and also chromosome 10q26 have strongly been elicited to predispose individuals to the susceptibility to AMD. These polymorphisms have been verified in subsequent studies. However, results from different geographic regions of the world can represent discrepancies according to ethnic populations. Aforementioned genetic tests have been commercially introduced to give the patients the risk of progression to advanced stage of AMD, and rate of the risk can be given by the genetic results together with environmental factors in USA.

Age related macular degeneration is consisted of dry and wet forms. Although wet form is responsible from severe vision loss due to AMD, dry form can progress to wet form by passage of time. The risk of AMD increases when age get older and it causes very severe central vision loss; consequently reduces considerably the quality of life in senile population. Available treatment of AMD is expensive and has economical burden. Early diagnosis of the disease has favourable impact on post-treatment prognosis. Although the basis of treatment is primarily based on the preservation of current visual acuity, it is possible to obtain improvement in visual acuity with the agents inhibiting angiogenesis in recent years. However, complete response to the treatment is not obtained approximately in one fifth of the patients. Different responses to the treatment are obtained in the remaining group. The reason for the differences at the treatment may be due to different morphological subgroups and/or diversity of genetic variants in wet AMD. . We do not at the moment know whether gen polymorphisms related to AMD established in some western population are also related to AMD in our population or whether this relationship has similar risk or protective effect for AMD. The gen variants mostly studied in relation to AMD are CFH (rs1061170 and rs1410996), LOC387715/ARMS-2 (A69S /rs10490924), HTRA-1 (rs11200638), C3 (R102G/ rs2230199), C2 E318D (rs9332739), and CFB R32Q (rs641153). A preliminary study which was published recently, carried out by our team in a single center and in a small number of patients showed that CFH and LOC387715 gen polymorphisms entertain a risk for late AMD and suggested a necessity to perform a forward study with larger population to learn definite information about our population. On the other hand, the entire eight genetic locus related to AMD will be studied first time in our population. In the introduced projects study, the relationship of eight different gen polymorphisms (CFH rs1061170 and rs1410996, LOC387715 / ARMS2 gene rs10490924, C2 gene rs9332739, CFB gene rs641153, CFI rs10033900 , HTRA-1 gene rs11200638, C3 rs2230199) will be studied in 2800 patients with high risk intermediate and late stage AMD and 2200 age-matched control subjects. Blood samples from brachial veins of the study subjects will be collected in the 5 health centers composed of Bursa Retina Eye Center and Hospitals of Afyon Kocatepe University, Dokuz Eylul University, Konya University and Uludag University within the period of 32 months. After the collection of venous samples, polymorphisms will be genotyped by "real-time PCR'' and ''pyrosequencing" genotyping systems in the genetic laboratory of Afyon Kocatepe University Medical School. Within the last 3 months of the project duration, having completed genotyping of all samples, evaluation of the study data by clinically and statistically will be made, and preparation of final report will be realized. . As a primary outcome, protective effects or the risk rate of developing the late AMD for each genetic polymorphism will be calculated by statistical analysis following the genotyping. Sub-analyses will be done to investigate any relationship between genetic polymorphism and response to the treatment. Sub-analyses will be done to determine possible differences in genetic variants between the late dry and wet AMD and also among the morphological subtypes of the wet AMD. Main study and secondary sub-studies derived from sub-analyses by further methodology will be submitted as different studies for publication. The anticipated results of the study may have impact on the management and follow-up of the patients with AMD. Because AMD is etiologically multi-factorial disease and has environmental controllable risk factor outside the genotypic features, it may be possible to early diagnosis and frequent follow-up in addition to recommending to avoid from modifiable risk factors in patients with early AMD who are genetically under the high risk of the development of late AMD according to findings obtained from our study results. It will also be possible to establish the patients with wet AMD who are resistant or sensitive to the treatment according to genotyping. Whether performing genetic tests in patients who are candidate to the late AMD in the near future is significant and meaningful for our population will be established. Our results evaluated together with the literature will make substantial contribution to better understanding of pathogenesis of AMD as well as early diagnosis and better classification or treatment choices.

Study Type

Observational

Enrollment (Anticipated)

5000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Turkey
    • Afyon
      • Afyonkarahisar, Afyon, Turkey, 03200
        • Recruiting
        • Umit Ubeyt INAN
        • Contact:
        • Contact:
        • Principal Investigator:
          • Umit U INAN, MD
        • Principal Investigator:
          • Handan YILDIZUS, PhD
        • Principal Investigator:
          • Nilufer KOCAK, MD
        • Principal Investigator:
          • Banu OZTURK, MD
        • Principal Investigator:
          • Hurkan KERIMOGLU, MD
        • Principal Investigator:
          • Mujgan OZDEMIR, PhD
        • Principal Investigator:
          • Berkant KADERLI, MD
        • Principal Investigator:
          • Ozgur YALCINBAYIR, MD
        • Principal Investigator:
          • Mustafa DOGAN, MD
        • Principal Investigator:
          • Remzi AVCI, MD
        • Principal Investigator:
          • Suleyman KAYNAK, MD
        • Principal Investigator:
          • Suleyman DUNDAR, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with intermediate and advanced age related macular degeneration

Description

Inclusion Criteria:

  • Older age more than 50 years for the study group and older age more than 60 years for the control group
  • Intermediate or advanced stage age-related macular degeneration
  • Active or inactive scar choroidal neovascularization
  • For control patients: Normal macular anatomy and no sign of any stage of age-related macular degeneration

Exclusion Criteria:

  • People with findings of advanced age-related macular degeneration due to other reasons (inflammatory, myopic choroidal neovascularization etc..)
  • For control patients: Any sign of age-related macular degeneration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rate of homozygous, heterozygous or wild type genotype and allels
Time Frame: at the end of third years
Gene polymorphisms of 8 region with identification of homozygous, heterozygote and wild type genotyping and alleles
at the end of third years

Secondary Outcome Measures

Outcome Measure
Time Frame
Odds ratios for each genotyping in healthy elderly controls and patients with age related macular degeneration
Time Frame: at the end of third years
at the end of third years

Other Outcome Measures

Outcome Measure
Time Frame
Odds ratios for various combinations of gene regions between healthy elderly control and patients with age related macular degeneration
Time Frame: at the end of third years
at the end of third years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kocatepe University

Collaborators

The Scientific and Technological Research Council of Turkey

Investigators

  • Study Chair: Umit U INAN, MD, Kocatepe University Medical School Department of Ophthalmology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

November 1, 2017

Study Registration Dates

First Submitted

September 20, 2014

First Submitted That Met QC Criteria

September 20, 2014

First Posted (Estimate)

September 25, 2014

Study Record Updates

Last Update Posted (Estimate)

August 30, 2016

Last Update Submitted That Met QC Criteria

August 29, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0112S269

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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