Preeklamptik Hastalarda Adenozin Deaminaz Gen Polimorfizmi

Öz

Preeklampsi; hipertansiyon, proteinüri ve birçok klinik manifestasyon ile karakterize multisistem bir hastalıktır. Etyopatogenezi henüz tam olarak anlaşılamasa da azalmış plasental perfüzyonun genetik, immünolojik ve inflamatuar faktörlerden etkilendiği bilinmektedir. Preeklampside artan hücresel immünitenin temel mediatörlerinden adenozin deaminaz (ADA), pürin nükleotidlerinin yıkımında yer alan ve Adenozin’in İnozin’e çevrimini katalizleyen bir enzimdir. Preeklampside hücresel immünitenin artmasına bağlı olarak ADA seviyelerindeki artış saptanmıştır. Bu çalışmanın amacı preeklamptik hastalarda ADA gen polimorfizmini değerlendirmektir. Çalışmaya 45 asemptomatik normal gebe ile 43 preeklampsili gebe alındı. Olgulardan alınan maternal plazma örneklerinden PCR-RFLP (Polymerase Chain Reaction- Restriction fragment lenght polymorphism) tekniği ile 20. kromozom uzun kolu üzerinde bulunan ADA geninin 8. kodon kısmındaki 22. nükleotidinin G (Guanin)’den A (Adenin)’e dönmesi ile karakterize gen polimorfizmi incelendi. Her iki gruptan elde edilen verilerin istatistiksel analizi Fisher exact test ve Ki-kare testleri ile yapıldı. Her iki grup arasında psikososyokültürel ve demografik özellikler açısından fark saptanmadı. Kontrol grubundaki adenozin deaminaz gen polimorfizmi oranı %8,9 iken, preeklampsi grubundaki ADA gen polimorfizmi oranı %4,5 olarak saptandı. Preeklampsi grubu ile kontrol grubu arasında istatistiksel olarak anlamlı fark izlenmedi (p>0.05, Odds ratio: 0.9 [%95 confidence interval:0.485-1.693]). Çalışmanın sonucunda preeklamptik hastalardaki immünolojik patogenetik süreçlerin bir mediatörü olarak düşünülen ve pürin metabolizmasının en önemli enzimi olan adenozin deaminazı üreten ADA genindeki polimorfizmin, preeklamptik hastalarda farklı olmadığı görülmüştür. Maternal plazma ADA düzeyleri ile ilgili yapılan birçok çalışma olmasına rağmen, literatürde preeklamptik hastalarda ADA gen polimorfizmini ilk defa araştıran bu çalışma ile, preeklampsinin patogenezini için yapılacak ileri dönem araştırmalara bir katkı sağlayabileceğimizi ümit ediyoruz.

Anahtar Kelimeler

• Adenozin deaminaz,Preeklampsi,Gen polimorfizmi

Adenosine Deaminase Gene Polymorphism in Preeclampsia

Öz

Preeclampsia is a severe pregnancy complication characterized by high blood pressure and signs of damage to another organ system. Although the etiopathogenesis of the preeclampsia has not been fully understood, decreased placental perfusion resulting genetic, immunological and inflammatory factors is known to be the main cause. Increased cellular immunity in preeclampsia is a well-known immune response. One of the essential mediators in the cellular immune system is Adenosine deaminase (ADA). This enzyme involves in purine metabolism and catalyzes the irreversible deamination of adenosine and 2’-deoxyadenosine to inosine and 2’-deoxyinosine, respectively. Depending on the increase of cellular immunity in preeclampsia, earlier studies found increased levels of adenosine deaminase. This study aimed to evaluate the ADA gene polymorphism in preeclamptic women. 45 asymptomatic pregnant and 43 preeclamptic patients were included in the study. We investigated the ADA gene -located on the long arm of chromosome 20- codon 8, G22A polymorphism (Asp8Asn). There were no demographic differences between the two groups. The ADA gene polymorphism rate in the control group was 8.9%, while it was 4.5% in the preeclampsia group. Although this difference was not statistically significant and further studies are needed, ADA gene polymorphism in preeclamptic women has been investigated for the first time with this study in the medical literature.

Anahtar Kelimeler

• Adenosine deaminase,Preeclampsia,Gene Polymorphism

Kaynakça

1. 1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365: 785-99.
2. 2. Martin JA, Hamilton BE, Ventura SS, Menacker F, Park MM, Sutton PD. Births: Final data for 2001. Natl Vital Stat Rep 2002 Dec 18; 51:1-102.
3. 3. Sağlık İstaistikleri Yıllığı. Türkiye Cumhuriyeti Sağlık Bakanlığı 2009 www.saglik.gov.tr
4. 4. Redman CW, Sacks GP, Sargent IL. Preeclampsia: An excessive maternal inflammatory response to pregnancy Am J Obstet Gynecol 1999; 180:499-506.
5. 5. Bulla R, Bossi F, Agostinis C, Tedesco F. The multiple functions of the complement system in pregnancy. Am J Reprod Immunol 2006; 56:24-5.
6. 6. Borzychowski AM, Sargent IL, Redman CW. Inflammation and pre-eclampsia. Semin Fetal Neonatal Med 2006; 11:309-16.
7. 7. Redman CWG, Sargent IL. Preeclampsia, the placenta and the maternal systemic inflammatory response – a review. Placenta 2003;24(Suppl A):21-7.
8. 8. Adams A, Harkness RA. Adenosine deaminase activity in thymus and human tissues. Clin Exp Immunol 1976; 26:647–9.

9. 9. Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R, Camaioni E. Adenosine deaminase: functional implications and different classes of inhibitors. Med Res Rev 2001; 21:105–28.
10. 10. Conlon BA, Law WR. Macrophages are a source of extracellular adenosine deaminase-2 during inflammatory responses. Clin Exp Immunol 2004; 138:14–20.
11. 11. Kato H, Yoneyama Y, Araki T. Fetal plasma lipid peroxide levels in pregnancies complicated by preeclampsia. Gynecol Obstet Invest 1997; 43:158–61.
12. 12. Davidge ST, Signorella AP, Lykins DL, Gilmour CH, Roberts JM. Evidence of endothelial activation and endothelial activators in cord blood of infants of preeclamptic women. Am J Obstet Gynecol 1996; 175:1301–6.
13. 13. Friedman SA, Schiff E, Emeis JJ, et al. Fetal plasma levels of cellular fibronectin as a measure of fetal endothelial involvement in preeclampsia. Obstet Gynecol 1997;89:46–8.
14. 14. Yoneyama Y, Sawa R, Suzuki S, et al. Serum adenosine deaminase activity in women with preeclampsia. Gynecol Obstet Invest 2002; 54:164-7.
15. 15. Yoneyama Y, Sawa R, Suzuki S, et al. Relationship between plasma malondialdehyde levels and adenosine deaminase activities in preeclampsia. Clin Chim Acta 2002; 322:169–73.
16. 16. Karabulut AB, Kafkaslı A, Burak F, Gözükara EM. Maternal and fetal plasma adenosine deaminase, xsantine oxidase and malondialdehyde levels in preeclampsia. Cell Biochem Funct 2005; 23:279-83.
17. 17. Suzuki S, Yoneyama Y, Sawa R, Araki T. Relation between maternal serum adenosine deaminase and plasma adenosine levels in twin pregnancies. Clin Biochem 2002; 35:417-9.
18. 18. American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122:1122.
19. 19. Napolioni V, Lucarini N. Gender-specific association of ADA genetic polymorphism with human longevity. Biogerontology 2010; 11:457-62.
20. 20. Yoneyama Y, Sawa R, Suzuki S, Shin S, Power GG, Araki T. The relationship between uterine artery doppler velocimetry and umblical levels in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 1996;174(1Pt1):267-71.
21. 21. Suzuki S, Yoneyama Y, Sawa R, Takeuchi T, Power GG, Araki T. Maternal plasma adenosine levels in pregnancies complicated by toxemia. Placenta 1999; 13:407-14.
22. 22. Yoneyama Y, Suzuki S, Sawa R, Otsubo Y, Power GG, Araki T. Plasma adenosine levels increase in women with normal pregnancies. Am J Obstet Gynecol 2000; 182:1200-3.
23. 23. Suzuki S, Yoneyama Y, Sawa R, Araki T. Relation between serum uric acid and plasma adenosine levels in twin pregnancies. Obstet Gynecol 2000; 96:507-10.
24. 24. Suzuki S, Yoneyama Y, Sawa R, Otsubo Y, Takeuchi T, Araki T. Relation between serum uric acid and plasma adenosine levels in women with preeclampsia. Gynecol Obstet Invest 2001; 51:169-72.
25. 25. Yoneyama Y, Sawa R, Suzuki S, et al. Regulation of plasma adenosine levels in normal pregnancy. Gynecol Obstet Invest 2002; 53:71-4.
26. 26. Yoneyama Y, Sawa R, Suzuki S, et al. Relation between adenosine deaminase activities and cytokine-prodicing T cells in women with preeclampsia. Clin Biochem 2002; 35:303-6.
27. 27. Suzuki S, Kuwajima T, Yoneyama Y, Sawa R, Araki T. Maternal peripheral T-helper 1-type and T-helper 2-type immunity in nonpreeclamptic twin pregnancies. Gynecol Obstet Invest 2002; 53:140-3.
28. 28. Suzuki S, Yoneyama Y. Role of adenosine in regulation of uterine blood flow during nonpreeclamptic twin gestation. Tohoku J Exp Med 2003; 201:127-30.
29. 29. Kafkaslı A, Karabulut AB, Atmaca R, Laurini R. Clinical correlation between adenosine deaminase activity and preeclampsia severity. J Int Med Res 2006; 34:247-55.
30. 30. Bottini N, De Luca D, Saccucci P, et al. Autism: evidence of association with adenosine deaminase genetic polymorphism Neurogenetics 2001; 3:111–3.
31. 31. Hettinger JA, Liu X, Jeltje J, Holden A. The G22A Polymorphism of the ADA Gene and Susceptibility to Autism Spectrum Disorders. J Autism Dev Disord 2008; 38:14–9.
32. 32. Nicotra M, Bottini N, La Torre M et al. Repeated Spontaneous Abortion. Cooperative Effects of ADA and ACP1 Genetic Polymorphisms. Am J Reprod Immunol 2007;58:1–10.
33. 33. Kim SH, Kim YK, Park HW, et al. Adenosine deaminase and adenosine receptor polymorphisms in aspirin-intolerant asthma. Respir Med 2009; 103:356-63.
34. 34. Riksen NP, Franke B, van den Broek P, et al. The 22G>A polymorphism in the adenosine deaminase gene impairs catalytic function but does not affect reactive hyperaemia in humans in vivo. Pharmacogenetics and Genomics 2008; 18:843–6.
35. 35. Napolioni V, Predazzi IM. Age and gender-specific association between ADA (22G>A) and TNF-α (-308G>A) genetic polymorphisms. Tissue Antigens 2010;76(4):311-4.