Özgür TURGUT, Ümit LÜLEYAP, Mehmet Ali ERKOÇ, Perçin PAZARCI, Gülsevinç AY

İnterlökin-2 promotoru polimorfizmi ile preeklampsi arasındaki ilişki

Amaç: İmmün sistemde sistemde rol alan sitokinlerden biri de interlökin-2'dir. IL-2 geninin promotor bölgesindeki polimorfizmlerin preeklampsi ile sonuçlanan anormal plasentasyon ile ilişkilendirilen maternal savunma mekanizmasındaki belirleyici faktörlerden biri olabileceği ihtimali düşünülmektedir. Bu çalışmada preeklamptik Türk kadınlarında interlökin 2 geninin promotor bölgesindeki -384 polimorfizmi çalışılarak genotiplendirme yapılmış ve hangi genotipin koruyucu olduğu belirlenmeye çalışılmıştır.Gereç ve Yöntem: 57 normal, 89 preeklampsi olmak üzere toplam 146 birbiri ile akraba olmayan kadından kan alındı. IL-2 geninin -384 promotor bölgesi PCR yöntemi ile amplifiye edildi ve polimorfizmlerin tespiti için Restriction Fragment Length Polymorphism yöntemi Bfa-1 enzimi kullanılarak gerçekleştirildi.Bulgular: Çalışmaya dahil edilen 89 preeklamptik kadından 38’inin TT, 36’sının GT, 15’inin GG; 57 normal gebe kadından 28’inin TT, 22’sinin GT ve 7’sinin GG alleline sahip olduğu tespit edilmiştir.Sonuç: Preeklampsi hastalığının immün sistem ve inflamasyon cevabıyla olan yakın ilişkisi göz önünde bulundurularak, bu çalışmada IL-2 geni -384 promotor bölgesi polimorfizmi ile preeklampsi ilişkisinin araştırılması amaçlanmıştır. Genotipler arasında istatistiksel olarak anlamlı bir fark bulunamamıştır. Plasenta oluşumuna etkili olan tüm olumsuz faktörlerin dâhil edildiği genetik tabanlı kapsamlı araştırmaların yararlı olacağını düşünmekteyiz.

Anahtar Kelimeler:

RFLP, Preeklampsi, interlökin-2, polimorfizm

Relationship between interleukin-2 promoter polymorphism and preeclampsia

Purpose: One of the cytokines involved in the immune system is interleukin-2 (IL-2). It is contemplated that polymorphisms in the promoter region of the IL-2 gene may be one of the determining factors in the maternal immunization system associated with abnormal placentation resulting in preeclampsia. This study tried to determine the protective genotypes for preeclampsia by genotyping the -384 polymorphisms in the promoter region of interleukin 2 gene in preeclamptic Turkish women.Material and Methods: 146 blood samples, 57 normal and 89 preeclampsia, were collected from unrelated pregnant women. -384 promoter region of IL-2 gene is amplified by using PCR and Restriction Fragment Length Polymorphism method is applied by using Bfa-1 enzyme to identify the polymorphisms.Results: Of the 89 preeclamptic women included in the study, 38 had TT, 36 had GT, 15 had GG alleles and of the 57 normal pregnant women, 28 had TT, 22 had GT, and 7 had GG alleles.Conclusion: Considering the close relationship of preeclampsia with the immune system and the response to inflammation, this study aimed to investigate the relationship between IL-2 gene -384 promoter region polymorphism and preeclampsia. No statistically significant relationship was found between the genotypes. We think that comprehensive genetic studies including all negative factors that are effective for placenta formation would be useful.

Keywords:

RFLP, Preeclampsia, interleukin-2, polymorphism,

PDF

___

1. Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension. 2005;46:1243-9.
2. Roberts JM, Lain KY. Recent insights into the pathogenesis of pre-eclampsia. Placenta. 2002;23:359-72.
3. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357:53-6.
4. Witlin DOAG, Sibai MDBM. Hypertension in pregnancy: current concepts of preeclampsia. Annu Rev Med. 1997;48:115-27.
5. Mütze S, Rudnik-Schöneborn S, Zerres K, Rath W. Genes and the preeclampsia syndrome. J Perinat Med. 2008;36:38-58.
6. Chappell S, Morgan L. Searching for genetic clues to the causes of pre-eclampsia. Clin Sci. 2006;110:443- 58.
7. Matthiesen L, Berg G, Ernerudh J, Ekerfelt C, Jonsson Y, Sharma S. Immunology of preeclampsia. Chem Immunol Allergy. 2005;89:49-61.
8. de Groot CJM, Jansen MWJC, Bertina RM, Schonkeren JJM, Helmerhorst FM, Huizinga TWJ. Interleukin 10-2849AA genotype protects against pre-eclampsia. Genes Immun. 2004;5:313-4.
9. Ciarmela P, Boschi S, Bloise E, Marozio L, Benedetto C, Castellucci M et al. Polymorphisms of FAS and FAS ligand genes in preeclamptic women. Eur J Obstet Gynecol Reprod Biol. 2010;148:144-6.
10. Pazarbasi A, Kasap M, Guzel AI, Kasap H, Onbasioglu M, Ozbakir B et al. Polymorphisms in the tumor necrosis factor-alpha gene in Turkish women with pre-eclampsia and eclampsia. Acta Med Okayama. 2007;61:153-60.
11. Matesanz F, Fedetz M, Collado-Romero M, Fernández O, Guerrero M, Delgado C et al. Allelic expression and interleukin-2 polymorphisms in multiple sclerosis. J Neuroimmunol. 2001;119:101-5.
12. Laivuori H, Kaaja R, Ylikorkala O, Hiltunen T, Kontula K. 677 C→T polymorphism of the methylenetetrahydrofolate reductase gene and preeclampsia. Obstet Gynecol. 2000;96:277-80.
13. Zusterzeel PL, Peters WH, Visser W, Hermsen KJ, Roelofs HM, Steegers EA. A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia. J Med Genet. 2001;38:234-7.
14. Steegers EAP, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376:631- 44.
15. Barton JR, Sibai BM. Prediction and prevention of recurrent preeclampsia. Obstet Gynecol. 2008;112:359-72.
16. Rijhsinghani A. Risk of preeclampsia in secondtrimester triploid pregnancies. Obstet Gynecol. 1997;90:884-8.
17. Julian CG. High altitude during pregnancy. Clin Chest Med. 2011;32:21-31.
18. Haukim N, Bidwell JL, Smith AJP, Keen LJ, Gallagher G, Kimberly R et al. Cytokine gene polymorphism in human disease: on-line databases, Supplement 2. Genes Immun. 2002;3:313-30.
19. Daher S, Shulzhenko N, Morgun A, Mattar R, Rampim GF, Camano L et al. Associations between cytokine gene polymorphisms and recurrent pregnancy loss. J Reprod Immunol. 2003;58:69-77.
20. Speer EM, Gentile DA, Zeevi A, Pillage G, Huo D, Skoner DP. Role of single nucleotide polymorphisms of cytokine genes in spontaneous preterm delivery. Hum Immunol. 2006;67:915-23.
21. Choi YK, Kwak-Kim J. Cytokine gene polymorphisms in recurrent spontaneous abortions: a comprehensive review. Am J Reprod Immunol. 2008;60:91-110.
22. de Lima THB, Sass N, Mattar R, Moron AF, Torloni MR, Franchim CS et al. Cytokine gene polymorphisms in preeclampsia and eclampsia. Hypertens Res. 2009;32:565-9.
23. Vural P, Degirmencioglu S, Saral NY, Demirkan A, Akgul C, Yildirim G et al. Tumor necrosis factor α, interleukin-6 and interleukin-10 polymorphisms in preeclampsia. J Obstet Gynaecol Res. 2010;36:64-71.
24. Lachmeijer AMA, Dekker GA, Pals G, Aarnoudse JG, ten Kate LP, Arngrı́msson R. Searching for preeclampsia genes: the current position. Eur J Obstet Gynecol Reprod Biol. 2002;105:94-113.
25. Laivuori H. Genetic aspects of preeclampsia. Front Biosci. 2007;12:2372.
26. Cross JC. The genetics of pre-eclampsia: a fetoplacental or maternal problem? Clin Genet. 2003;64:96-103.
27. Mutze S, Rudnik-Schoneborn S, Zerres K, Rath W. Genes and the preeclampsia syndrome. J Perinat Med. 2008;36:38-58.
28. Uzan J, Carbonnel M, Piconne O, Asmar R, Ayoubi JM. Pre-eclampsia: pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467- 74