Związek polimorfizmu 762Val/Ala genu ADPRT z ryzykiem występowania jaskry pierwotnej otwartego kąta w populacji polskiej
Association of the 762 Val/Ala ADPRT Gene Polymorphism with a Risk of Primary Open-angle Glaucoma Development in a Polish Population
Magda Cuchra1, Ireneusz Majsterek1, Karolina Przybyłowska1, Mira Gacek2, Jerzy Szaflik2, Jacek P. Szaflik2
1 Zakład Chemii i Biochemii Klinicznej Uniwersytetu Medycznego w Łodzi
Kierownik: dr hab. Ireneusz Majsterek, prof. nadzw. UM w Łodzi
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: Glaucoma is a heterogeneous group of ocular diseases that is characterized by progressive degeneration of the optic nerve and loss of visual field. It is estimated that glaucoma is one of the main reason of blindness in development countries. It is estimated that more than 750 000 people may by affected by glaucoma in Poland. In spite of wide research on cause of primary open angle glaucoma (POAG) development, the multi – factorial etiology of this disease has not been clearly understood yet. Recent studies have shown that reactive oxygen species (ROS) may play important role in the pathogenesis of POAG. Same data have postulated that oxidative DNA lesions are significant increased in human trabecular meshwork among patients affected POAG compared to healthy controls. Therefore in this project we focus on base excision repair pathway the main mechanisms that is responsible of removing oxidative DNA lesion. That is why the aim of this study was to evaluate an association between the 762Val/Ala ADPRT gene polymorphism with a risk of POAG development in a Polish population.
Material and Methods: One hundred thirty-four patients with POAG (mean age 72 ± 10) and one hundred forty-five healthy case controls (mean age 67 ± 12) were enrolled in our study. Gene polymorphism was analyzed by PCR-reaction fragment length polymorphisms (PCR-RFLP). PCR product was digested overnight with specific restriction endonucleases of BstU1 for the 762Val/Ala ADPRT gene polymorphism.
Results: We showed that the 762Val/Ala ADPRT genotype [OR 2.15, 95% CI (1.27–3.63); p<.0001] was associated with an increase risk of POAG. Additionally, we showed that the 762Ala allel [OR 1.76, 95% CI (1.17–2.66); p = 0,007] may be also associated with a increase risk of POAG development.
Conclusion: In conclusion, we suggest that the 762Val/Ala ADPRT gene polymorphism encoding main enzyme of base excision repair pathway may be an important risk factor of POAG development in a Polish population.
Słowa kluczowe: jaskra pierwotna otwartego kąta, DNA, uszkodzenia oksydacyjne DNA, naprawa przez wycinanie zasad azotowych.
Keywords: primary open angle glaucoma, DNA, oxidative DNA damage, base excision repair.