Anjiyotensin II tip 2 reseptör geni (AGTR2) ve interlökin 4 (IL-4) genindeki tek nükleotid polimorfizmlerinin preeklampsi riskine katkılarının Türk populasyonunda incelenmesi

Year 2017, Volume: 42 Issue: 3, 477 - 483, 30.09.2017

Lütfiye Özpak Ayfer Pazarbaşı Nurşen Keser M. Bertan Yılmaz H. Ümit Lüleyap Fatime Tuncay Özgünen

https://doi.org/10.17826/cutf.297910

Abstract

Amaç: Preeklampsi, tüm gebeliklerin yaklaşık %6-10’ unda görülen ve gebe kadınlara özgü ciddi bir hastalıktır. İmmün ve genetik faktörlerin de katkıda bulunduğu kompleks bir hastalıktır. Bu çalışmada amacımız, AGTR2A1675G ve IL4 -590 (C>T) polimorfizmleri ve preeklampsi arasında bir ilişki olup olmadığını incelemekti.

Gereç ve Yöntem: Yüz otuzbir preeklampsili ve 86 normal gebe kadından alınan periferik kandan, genomic DNA izole edildi.  AGTR2 ve IL-4 polimorfizmleri polimeraz zincir reaksiyonu kullanılarak genotiplendirildi.

Bulgular: AGTR2 geni 1675 polimorfizminin genotip frekansı açısından önemli bir fark bulunamadı fakat allel frekansları açısından önemli bir fark bulunmuştur. IL-4 geni -590 polimorfizmi genotip ve allel frekansları açısından önemli bir fark bulunamamıştır.

Sonuç: AGTR2, GG genotipi ve IL-4, TT genotipi preeklampsili kadınlarda normal gebe kadınlara oranla önemli derecede yüksek bulundu. Bu genotipe sahip olma, preeklampsi meydana gelmesi açısından bir risk faktörü olabilir ancak bu bulgular daha fazla örnekte test edilmeye ihtiyaç duymaktadır. 

Keywords

IL-4, Preeklampsi, AGTR2, polimorfizm.

Evaluation of single nucleotide polymorphisms of angiotensin II type 2 receptor (AGTR2) gene and interleukin 4 (IL-4) gene for their contribution to the risk of preeclampsia in Turkish population

Abstract

Purpose: Preeclampsia, specific to human pregnancies, is a serious disorder, which occurs approximately in 6-10% of all pregnancies. It is a complex disorder, in which immune and genetic factors also take part. The aim of the current study was toinvestigate whether there is an association between AGTR2 A1675G and IL4 -590 (C>T) polymorphisms and preeclampsia.

Material and Methods: Genomic DNA was extracted from the peripheral venous blood of 131 preeclamptic and 86 normotensive pregnant women. The AGTR2 and IL-4 polymorphisms were genotyped by using a polymerase chain reaction assay.

Results: As for AGTR2 gene 1675 polymorphism, there was not any significant difference in terms of genotype frequencies but there was a significant difference in terms of allele frequencies. As for IL-4 gene -590 polymorphism, there was not any significant difference in terms of genotype and allele frequencies.

Conclusions: AGTR2, GG genotype and IL-4, TT genotype were found significantly higher in preeclamptic women than normotensive pregnant women.These genotypes might be a susceptibility risk factor for preeclampsia but these findings need to be tested in a larger sample size.

Keywords

IL-4, Preeclampsia, AGT2R, polymorphism

References

• 1. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003;102:181-92.
• 2. Roberts CB, Rom L, Moodley J, Pegoraro RJ Hypertension-related gene polymorphisms in pre-eclampsia, eclampsia and gestational hypertension in Black South African women. J Hypertens. 2004;22:945-8.
• 3. Hernandez-Diaz S, Toh S, Cnattingius S. Risk of preeclampsia in first and subsequent pregnancies: prospective cohort study. BMJ. 2009;338:b2255.
• 4. Williams PJ, Broughton Pipkin F. The genetics of pre-eclampsia and other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25:405-17.
• 5. Nielsen AH, Schauser KH, Poulsen K. Current topic: the uteroplacental renin-angiotensin system. Placenta. 2000;21:468-77.
• 6. Volpe M, Savoia C, De Paolis P, Ostrowska B, Tarasi D, Rubattu S. The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease. J Am Soc Nephrol. 2002;3:173-8.
• 7. Zhang Y, Zhang KX, Wang GL, Huang W, Zhu DL. Angiotensin II type 2 receptor gene polymorphisms and essential hypertension. Acta Pharmacol Sin. 2003;24:1089-93.
• 8. Gonzalez M, Lobos L, Castillo F, Galleguillos L, Lopez NC, Michea L. High-salt diet inhibits expression of angiotensin type 2 receptor in resistance arteries. Hypertension. 2005;45: 853-9.
• 9. Takeda-Matsubara Y, Iwai M, Cui TX, Shiuchi T, Liu HW, Okumura M et al. Roles of angiotensin type 1 and 2 receptors in pregnancy-associated blood pressure change. Am J Hypertens. 2004;17:684-9.
• 10. Akbar SA, Khawaja NP, Brown PR, Tayyeb R, Bamfo J, Nicolaides KH. Angiotensin II type 1 and 2 receptors gene polymorphisms in pre-eclampsia and normal pregnancy in three different populations. Acta Obstet Gynecol Scand. 2009;88: 606-11.
• 11. Kang L, Chen CH, Yu CH, Chang CH, Chang FM. An association study of interleukin-4 gene and preeclampsia in Taiwan. Taiwan J Obstet Gyneco. 2014;53:215-9.
• 12. Salimi S, Mohammadoo-Khorasani M, Yaghmaei M, Mokhtari M, Moossavi M. Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia. Biomed Res Int. 2014;497031.
• 13. Saito S, Shiozaki A, Nakashima A, Sakai M, Sasaki Y. The role of the immune system in preeclampsia. Mol Aspects Med. 2007;28:192-209.
• 14. Pazarbaşi A, Kasap M, Güzel AI, Kasap H, Onbaşioğlu 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.
• 15. Vural P, Degirmencioglu S, Saral NY, Demirkan A, Akgul C, Yildirim G et al. Tumor necrosis factor alpha, interleukin-6 and interleukin-10 polymorphisms in preeclampsia. J Obstet Gynaecol Res. 2010;36:71-64.
• 16. Miller SA, Dykes DD, Polesky HF A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
• 17. National High Blood Pressure Education Program Working Group. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000;183:S1-22.
• 18. Jafari M, Nasiri MR, Sanaei R, Anoosheh S, Farnia P, Sepanjnia A et al.. The NRAMP1, VDR, TNFα, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: a case-control study. Infect Genet Evol. 2016;39:92-8.
• 19. Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Gene. 2000;91:256-60.
• 20. Rahimi Z, Mansouri Zaveleh O, Rahimi Z, Abbasi A. AT2R -1332 G: a polymorphism and diabetic nephropathy in type 2 diabetes mellitus patients. J Renal Inj Prev. 2013;2:101-97.
• 21. Rahimi Z, Rahimi Z, Aghaei A, Vaisi-Raygani A. AT2R -1332 G:A polymorphism and its interaction with AT1R 1166 A:C, ACE I/D and MMP-9 -1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia. Gene. 2014;538:176-81.
• 22. Zhou A, Dekker GA, Lumbers ER, Lee SY, Thompson SD, McCowan LM et al. The association of AGTR2 polymorphisms with preeclampsia and uterineartery bilateral notching is modulatedby maternal BMI. Placenta. 2013;34:81-75.
• 23. Plummer S, Tower C, Alonso P, Morgan L, Baker P, Broughton-Pipkin F et al. Haplotypes of the angiotensin II receptor genes AGTR1 and AGTR2 in women with normotensive pregnancy and women with preeclampsia. Hum Mut. 2004;24:14-20.
• 24. Li Y, Zhu M, Hu R, Yan W. The effects of gene polymorphisms in angiotensin II receptors on pregnancy-induced hypertension and preeclampsia: a systematic review and meta-analysis. Hypertens Pregnancy. 2015;34:241-60.
• 25. Atanasovska-Stojanovska A, Trajkov D, Nares S, Angelov N, Spiroski M. IL4 gene polymorphisms andtheir relation to periodontal disease ina Macedonian populationHum Immunol. 2011;72:446-50.
• 26. Zhang Z, Wang L, Sun X, Zhang L, Lu L. Association of IL4 and IL4R polymorphisms with multiple sclerosis susceptibility in Caucasian population: a meta-analysis. J Neurol Sci. 2016;363:107-13.
• 27. Fraser R, Walker JJ, Ekbote UV, Martin KL, McShane P, Orsi NM. Interleukin-4 -590 (C>T), toll-like receptor-2 +2258 (G>A) and matrix metalloproteinase-9 -1562 (C>T) polymorphisms in pre-eclampsia. BJOG. 2008;115:1052