Volume 24, Number 12 (Feb-Mar 2017)                   JSSU 2017, 24(12): 1004-1012 | Back to browse issues page


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Shahbazi S, Torfeh M. Exploring the Link between ACE Insertion/Deletion (I/D) Polymorphism and Uterine Leiomyomas. JSSU. 2017; 24 (12) :1004-1012
URL: http://jssu.ssu.ac.ir/article-1-3564-en.html

Abstract:   (796 Views)

Introduction: Uterine leiomyomas arise from the proliferation of smooth muscle cells. ACE gene encodes a convertase enzyme mainly secreted in vascular endothelial cells which is involved in the renin–angiotensin system and blood pressure controlling. This gene has an insertion/deletion (I/D) polymorphism correlates to serum and tissue ACE levels. The aim of this study is to elucidate the relationship between ACE gene variation and the development of myom.

Methods: The samples of 55 uterine leiomyoma patients and 78 healthy women were studied. After obtaining informed consent, blood samples were collected and DNA extraction was performed by Salting-out method. Genotyping was performed using PCR reaction. The amplified products were two bands of 190 and 490 bp, which represents D allele and I allele, respectively. Statistical analysis was done using Chi-square test.

Results: The D allele frequency was 0.55 in the patient group and 0.51 in the control group. The I allele frequencies in the two groups were 0.45 and 0.49, respectively. The results showed that taking the II genotype into account as reference genotype; homozygous DD individuals were at increased risk of uterine myoma (Odds ratio: 1.37). However, heterozygous ID showed a similar risk with the II genotype as the reference group.

Conclusion: High blood pressure is significantly associated with uterine fibroids. It has been shown that atherosclerotic damage of uterine blood vessels and the inflammatory process caused by it may play an important role in the development of uterine myoma. This study indicates a positive relationship between the ACE (I/D) polymorphism and the risk of uterine myoma. This finding is evidence of the important role of the renin–angiotensin system in the pathogenesis of myoma

Full-Text [PDF 602 kb]   (345 Downloads)    
Type of Study: Original article | Subject: Genetics
Received: 2016/01/11 | Accepted: 2016/09/24 | Published: 2017/05/7

References
2. Ferenczy A, Richart RM, Okagaki T. A comparative ultrastuctural study of leiomyosarcoma, cellular leiomyoma, and leiomyoma of the uterus. Cancer 1971; 28(4): 1004-18.
3. Kawaguchi K, Fujii S, Konishi I, Nanbu Y, Nonogaki H, Mori T. Mitotic activityin uterine leiomyomas during the menstrual cycle. Am J Obstet Gynecol 1989; 160(3): 637-41.
4. Schaffer JI, Wai CY, Boreham MK. Etiology of pelvic organ prolapse. Clin Obstet Gynecol 2005; 48(3): 639-47.
5. Zupi E, Sbracia M, Marconi D, Munro MG. Myolysis of uterine fibroids: is there a role? Clin Obstet Gynecol 2006; 49(4): 821-33.
6. Flake GP, Andersen J, Dixon D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect 2003; 111(8): 1037-54.
7. Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation. American journal of epidemiology 2001; 153(1): 9-11.
8. Marshall LM, Spiegelman D, Goldman MB, Manson JE, Colditz GA, Barbieri RL, et al. A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertil Steril 1998; 70(3): 432-439.
9. Jia H, Wang B, Yu L, Jiang Z. Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with polycystic ovary syndrome: a meta-analysis. Journal of the renin-angiotensin-aldosterone system: JRAAS 2013; 14(3): 255-262.
10. Puthucheary Z, Skipworth JR, Rawal J, Loosemore M, Van Someren K, Montgomery HE. The ACE gene and human performance: 12 years on. Sports medicine 2011; 41(6): 433-448.
11. Zhang Z, Xu G, Liu D, Fan X, Zhu W, Liu X. Angiotensin-converting enzyme insertion/deletion polymorphism contributes to ischemic stroke risk: a meta-analysis of 50 case-control studies. PloS one 2012; 7(10): e46495.
12. Yu ZY, Chen LS, Zhang LC, Zhou TB. Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy. Nephrology 2012; 17(5): 480-487.
13. Blake RE. Leiomyomata uteri: hormonal and molecular determinants of growth. J Natl Med Assoc 2007; 99(10): 1170-1184.
14. Luo X, Chegini N. The expression and potential regulatory function of microRNAs in the pathogenesis of leiomyoma. Semin Reprod Med 2008; 26(6): 500-514.
15. Heinonen HR, Sarvilinna NS, Sjoberg J, Kampjarvi K, Pitkanen E, Vahteristo P, et al. MED12 mutation frequency in unselected sporadic uterine leiomyomas. Fertil Steril 2014; 102(4): 37-42.
16. Makinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 2011; 334(6053): 252-255.
17. Shahbazi S, Fatahi N, Amini-Moghaddam S. Somatic mutational analysis of MED12 exon 2 in uterine leiomyomas of Iranian women. American journal of cancer research 2015; 5(8): 2441-2446.
18. Boynton-Jarrett R, Rich-Edwards J, Malspeis S, Missmer SA, Wright R. A prospective study of hypertensionand risk of uterine leiomyomata. American journal of epidemiology 2005; 161(7): 628-38.
19. Dinh DT, Frauman AG, Johnston CI, Fabiani ME. Angiotensin receptors: distribution, signalling and function. Clinical science 2001; 100(5): 481-492.
20. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. The Journal of clinical investigation 1990; 86(4): 343-346.
21. Hsieh YY, Lee CC, Chang CC, Wang YK, Yeh LS, Lin CS. Angiotensin I-converting enzyme insertion-related genotypes and allele are associated with higher susceptibility of endometriosis and leiomyoma. Molecular reproduction and development 2007; 74(7): 808-14.
22. Gultekin GI, Yilmaz SG, Kahraman OT, Atasoy H, Dalan AB, Attar R, et al. Lack of influence of the ACE1 gene I/D polymorphism on the formation and growth of benign uterine leiomyoma in Turkish patients. Asian Pacific journal of cancerprevention: APJCP 2015; 16(3):1123-7.
23. Moradzadegan A, Vaisi-Raygani A, Nikzamir A, Rahimi Z. Angiotensin converting enzyme insertion/deletion (I/D) (rs4646994) and Vegf polymorphism (+405G/C; rs2010963) in type II diabetic patients: Association withthe risk of coronary artery disease. J the renin-angiotensin-aldosterone system: JRAAS 2015; 16(3): 672-80.
24. Vaisi-Raygani A, Rahimi Z, Tavilani H, Vaisi-Raygani H, Kiani A, Aminian M, et al. Synergism between paraoxonase Arg 192 and the angiotensin converting enzyme D allele is associated with severity of coronary artery disease. Molecular biology reports 2012; 39(3): 2723-31.

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