Wydanie 1/2010
str. 63

Związek polimorfizmów -1296C>T i -915A>G genu tkankowego inhibitora metaloproteazy-3 (TIMP-3) ze zwyrodnieniem plamki związanym z wiekiem (AMD)

Association Between -1296C>T i -915A>G Polymorphisms of the Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) Gene and Age-related Macular Degeneration (AMD)

Katarzyna Janik-Papis1, Janusz Błasiak1, Małgorzata Zaraś2, Magdalena Ulińska2

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: Introduction: Age-related macular degeneration (AMD) is the most common cause of blindness in individuals aged over 50 in the developed countries. The tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of the matrix metalloproteinases, a group of zinc-binding endopeptidases involved in degradation of the extracellular matrix. Mutations in the TIMP-3 gene cause Sorsby fundus dystrophy (SFD), a hereditary macular degenerative disease characterized by extracellular matrix (ECM) irregularities in Bruch?s membrane. This disease has strong similarity to AMD. Moreover, eyes with AMD demonstrate accumulation of specific deposits and ECM molecules under the retinal pigment epithelium and metalloproteinases are crucial regulators of basement membrane and ECM turnover which are regulated by TIMP-3. Additionally TIMP-3 plays a protective role in wet AMD by inhibition of connecting VEGF-A with its receptor VEGFR2, which stops of choroidal neovascularization processes. Purpose: We investigated two polymorphisms in the promoter region of the TIMP-3 gene, -1296C>T and -915A>G, which may primarily affect the level of transcription, in wet and dry forms of AMD. Material and Methods: Genomic DNA was obtained from patients with wet form of AMD (n = 176), dry form of the disease (n = 79) and healthy individuals (n = 68). The genotypes of the -1269C>T and -915A>G polymorphisms of the TIMP-3 gene were determined by restriction fragment length polymorphism PCR with AluI and ApaI enzymes. Digested products were separated onto a 10% polyacrylamide gel. Results: We observed a strong association between the CC genotype (OR 5,06, 95% CI 2.54-10.01) and C allele (OR 4.4, 95% CI 2.93-6.61) of the -1296C>T polymorphism of the TIMP-3 gene and the occurrence of the AMD. On the other hand, the TT genotype (OR 0.16, 95% CI 0.09-0.29) and T allele (OR 0.23, 95% CI 0.15-0.34) protected against the AMD. We did not find any association between the -915A>G polymorphism and AMD, as well as between genotype and haplotype combination of these two polymorphisms and AMD. Conclusions: The ?1269C>T polymorphism of the TIMP-3 gene may modulate the susceptibility to the AMD, through the change in the expression of the gene, but we do not know how it could be linked to wet or dry form of this disease, because there is no statistical association with it. Further studies are needed.

Słowa kluczowe: zwyrodnienie plamki związane z wiekiem, AMD, tkankowy inhibitor metaloproteazy-3, TIMP-3, polimorfizm genetyczny

Keywords: age-related macular degeneration, AMD, tissue inhibitor of metalloproteinases-3, TIMP-3, genetic polymorphism


powrót

REDAKCJA NIE UDZIELA PORAD MEDYCZNYCH I NIE POŚREDNICZY W KONSULTACJACH PACJENTÓW Z LEKARZAMI