Wydanie 2/2011
str. 27

Znaczenie zmienności genów homeostazy żelaza w zwyrodnieniu plamki związanym z wiekiem

Role of Variability in Iron Homeostasis Genes in Age-related Macular Degeneration

Janusz Błasiak1, Jerzy Szaflik2, Jacek P. Szaflik2

1 Katedra Genetyki Molekularnej Uniwersytetu Łódzkiego
  Kierownik: prof. dr hab. Janusz Błasiak
2 Katedra i Klinika Okulistyki II Wydziału Lekarskiego Warszawskiego Uniwersytetu Medycznego
  Samodzielny Publiczny Kliniczny Szpital Okulistyczny w Warszawie
  Kierownik: prof. dr hab. n. med. Jerzy Szaflik


Summary: Purpose: Reactive oxygen species (ROS) may contribute to the pathogenesis of age-related macular degeneration (AMD). ROS can be produced in the Fenton reaction catalyzed by Fe3+ ions. Therefore, altered homeostasis of iron in the retina may be the source of ROS and its damage resulting in clinically detectable AMD symptoms. Genetic variability of the key components involved in iron transport and storage may change their functioning and in this way contribute to AMD. We studied the association between AMD and polymorphisms of several genes encoding proteins involved in iron homeostasis. Those included transferrin (TF) and its receptors (TFR1 and 2), hepcidin (HEMP), heme oxygenase-1 and 2 HMOX1 and 2, NAD(P)H: quinine oxidoreductase 1 (NQO1), nitric oxide synthase 3 (NOS3), nuclear factor erythroid2-related factor (Nrf2) and others.
Material and Methods: Polymorphisms were determined in the blood obtained from patients with dry and wet forms of AMD and sex- and age-matched. Genotyping was performed with allele-specific- and restriction fragment length polymorphism-polymerase chain reaction.
Results: We obtained several associations between the occurrence of AMD or either its form and genotypes of several polymorphisms of the iron homeostasis genes, including -576G>A-TF, 1892C>T-TFR2, 19G>C-HMOX1, -42+1444 A>G-HMOX2, 25129A>C-Nrf2, 894G>T-NOS3. These associations were either positive or negative and often depended on the form of the disease as well as several environmental and life-style factors, including age, sex, smoking, living environment.
Conclusion: Genetic variability in the components of iron homeostasis genes may be associated with AMD and results of research on this association may contribute to the conception of the microarray “Iron in AMD”.

Słowa kluczowe: zwyrodnienie plamki związane z wiekiem, AMD, zmienność genetyczna, żelazo, stres oksydacyjny.

Keywords: age-related macular degeneration, AMD, genetic variability, iron, oxidative stress.


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