Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.3.1123

Lack of Influence of the ACE1 Gene I/D Polymorphism on the Formation and Growth of Benign Uterine Leiomyoma in Turkish Patients  

Gultekin, Guldal Inal (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University)
Yilmaz, Seda Gulec (Department of Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University)
Kahraman, Ozlem Timirci (Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University)
Atasoy, Hande (Department of Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University)
Dalan, A. Burak (Yeditepe University Hospital, Faculty of Medicine, Yeditepe University)
Attar, Rukset (Department of Gynecology, Faculty of Medicine, Yeditepe University)
Buyukoren, Ahmet (Department of Gynecology, Faculty of Medicine, Istanbul University)
Ucunoglu, Nazli (Department of Molecular Medicine, Institute of Health Sciences, Faculty of Medicine, Yeditepe University)
Isbir, Turgay (Department of Medical Biology, Faculty of Medicine, Yeditepe University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.3, 2015 , pp. 1123-1127 More about this Journal
Abstract
Uterine leiomyomas (ULM), are benign tumors of the smooth muscle cells of the myometrium. They represent a common health problem and are estimated to be present in 30-70% of clinically reproductive women. Abnormal angiogenesis and vascular-related growth factors have been suggested to be associated with ULM growth. The angiotensin-I converting enzyme (ACE) is related with several tumors. The aim of this study was to identify possible correlation between ULM and the ACE I/D polymorphism, to evaluate whether the ACE I/D polymorphism could be a marker for early diagnosis and prognosis. ACE I/D was amplified with specific primer sets recognizing genomic DNA from ULM (n=72) and control (n=83) volunteers and amplicons were separated on agarose gels. The observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium ($x^2=2.162$, p=0.339). There was no association between allele frequencies and study groups ($x^2=0.623$; p=0.430 for ACE I allele, $x^2=0.995$; p=0.339 for ACE D allele). In addition, there were no significant differences between ACE I/D polymorphism genotype frequencies and ULM range in size and number ($X^2=1.760;$ p=0.415 for fibroid size, $X^2=0.342;$ p=0.843 for fibroid number). We conclude that the ACE gene I/D polymorphism is not related with the size or number of ULM fibroids in Turkish women. Thus it cannot be regarded as an early diagnostic parameter nor as a risk estimate for ULM predisposition.
Keywords
Angiogenesis; benign cancer; uterine fibroid; uterine myoma; ACE insertion/deletion;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Alvarez R, Terrados N, Ortolano R, et al (2000). Genetic variation in the renin-angiotensin system and athletic performance. Eur J Appl Physiol, 82, 117-120.   DOI
2 Ates O, Demirturk F, Toprak M, et al (2013). Polymorphism of catechol-o-methyltransferase and uterine leiomyoma. Mol Cell Biochem, 375, 179-83.
3 Baird DD, Dunson DB, Hill MC, et al (2000). High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol, 188, 100-7.
4 Bayram B, Kilicci C, Onlu H, et al (2011). Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and polycystic ovary syndrome (PCOS). Gene, 489, 86-8.   DOI
5 Cardozo ER, Clark AD, Banks NK, et al (2012). The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol, 206, 1-9.   DOI
6 Catherino WH, Eltoukhi HM, Al-Hendy A (2013). Racial and ethnic differences in the pathogenesis and clinical manifestations of uterine leiomyoma. Semin Reprod Med, 31, 370-9.   DOI
7 Cha PC, Takahashi A, Hosono N, et al (2011). A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat Genet, 43, 447-50.   DOI
8 Cheng Z, Ma R, Tan W, et al (2014). Lack of association between ACE insertion/deletion polymorphism and lung cancer: A meta-analysis. J Renin Angiotensin Aldosterone Syst, [Epub ahead of print].
9 Di Lieto A, De Falco M, Pollio F, et al (2005). Clinical response, vascular change, and angiogenesis in gonadotropin-releasing hormone analogue- treated women with uterine myomas. J Soc Gynecol Investig, 12, 123-8.   DOI
10 Dinh DT, Frauman AG, Johnston CI, et al (2001). Angiotensin receptors: distribution, signaling and function. Clin Sci (Lond), 100, 481-92.   DOI
11 Edwards TL, Michels KA, Hartmann KE, et al (2013). BET1L and TNRC6B associate with uterine fibroid risk among European Americans. Hum Genet, 132, 943-53.   DOI
12 Ekin M. Cengiz H, Ozturk E, et al (2014). Genitourinary symptoms and their effects on quality of life in women with uterine myomas. Int Urogynecol J, 25, 807-10.   DOI
13 Ergen HA, Hatemi H, Agachan B, et al (2004). Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients. Exp Mol Med, 36, 345-50.   DOI
14 Fernandez LA, Twickler J, Mead A (1985). Neovascularization produced by angiotensin II. J Lab Clin Med, 105, 141-5.
15 Fishchuk LE, Gorovenko NG (2013). Genetic polymorphisms of the renin-angiotensin system in breast cancer patients. Exp Oncol, 35, 101-4.
16 Flake GP, Andersen J, Dixon D (2003). Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect, 111, 1037-54.
17 Freitas-Silva M, Pereira D, Coelho C, et al (2004). Angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. Cancer Genet Cytogenet, 155, 42-6.   DOI
18 Henskens LH, Spiering W, Stoffers HE, et al (2003). Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the hippocates study. J Hypertens, 21, 81-6.   DOI
19 Gülec-Yilmaz S, Yilmaz H, Dalan AB, et al (2014). The relationship between ACE polymorphism and panic disorder. In Vivo, 28, 885-9.
20 Hakverdi S, Demirhan O, Tunc E, et al (2013). Chromosome imbalances and alterations in the p53 gene in uterine myomas from the same family members: familial leiomyomatosis in Turkey. Asian Pac J Cancer Prev, 14, 651-8.   DOI
21 Herr D, Bekes I, Wulff C (2013). Local renin-angiotensin system in the reproductive system. Front Endocrinol, 4, 1-7.
22 Hsieh YY, Lee CC, Chang CC, et al (2007). Angiotensin I-converting enzyme insertion-related genotypes and allele are associated with higher susceptibility of endometriosis and leiomyoma. Mol Reprod Dev, 74, 808-14.   DOI
23 Isbir SC, Tekeli A, Ergen A, et al (2007). Genetic polymorphisms contribute to acute kidney injury after coronary artery bypass grafting. Heart Surg Forum, 10, 439-44.
24 Jia H, Wang B, Yu L, et al (2013). Association of angiotensinconverting enzyme gene insertion/deletion polymorphism with polycystic ovary syndrome: a meta-analysis. J Renin Angiotensin Aldosterone Syst, 14, 255-62.   DOI
25 Li XL, Zheng ZJ, Qu HO (2014). Lack of association of angiotensin-converting enzyme insertion/deletion polymorphism with breast cancer: An update meta-analysis based on 10405 subjects. J Renin Angiotensin Aldosterone Syst, [Epub ahead of print].
26 Li ZH Pan XM, Han BW, et al (2012). No association between ACE polymorphism and risk of nasopharyngeal carcinoma. J Renin Angiotensin Aldosterone Syst, 13, 210-5.   DOI
27 Rigat B, Hubert C, Alhenc-Gelas F, et al (1990). An insertion/ deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest, 86, 1343-6.   DOI   ScienceOn
28 Liu SY, Sima X, Wang CH, et al (2011). The association between ACE polymorphism and risk of colorectal cancer in a Chinese population. Clin Biochem, 44, 1223-6.   DOI   ScienceOn
29 Matsumoto T, Sagawa N, Mukoyama M, et al (1996). Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy. J Clin Endocrinol Metab, 81, 4366-72.
30 Mc Menamin UC, Murray LJ, Cantwell MM, et al (2012). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review. Cancer Causes Control, 23, 221-30.   DOI
31 Rigat B, Hubert C, Corvol P, et al (1992). PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase. Nucleic Acids Res, 20,1433.
32 Risau W (1997). Mechanisms of angiogenesis. Nature, 386, 671-4.   DOI
33 Rocken C, Neumann K, Carl-McGrath S, et al (2007). The gene polymorphism of the angiotensin I-converting enzyme correlates with tumor size and patient survival in colorectal cancer patients. Neoplasia, 9, 716-22.   DOI
34 Shen Y, Ren ML, Xu J, et al (2014). A multicenter case-control study on screening of single nucleotide polymorphisms in estrogen-metabolizing enzymes and susceptibility to uterine leiomyoma in han chinese. Gynecol Obstet Invest, 77, 224-30.   DOI
35 Tal R, Segars JH (2014). The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy. Hum Reprod Update, 20, 194-216.   DOI
36 van der Knaap R, Siemes C, Coebergh JW, et al (2008). Reninangiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletionpolymorphism, and cancer: the Rotterdam Study. Cancer, 112, 748-57.   DOI   ScienceOn
37 The National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/gene/1636. Accessed January 2015.
38 Timmermans PB, Wong PC, Chiu AT, et al (1993). Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev, 45, 205-51.
39 Vairaktaris E, Serefoglou Z, Avgoustidis D, et al (2009). Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer. Oral Oncol, 45, 247-53.   DOI
40 Verit FF, Yucel O (2013). Endometriosis, leiomyoma and adenomyosis: the risk of gynecologic malignancy. Asian Pac J Cancer Prev, 14, 5589-97.   DOI
41 Wei MT, Chen N, He YZ, et al (2014). Angiotensin-converting enzyme insertion/deletion polymorphism and gastric cancer: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol, [Epub ahead of print].
42 Yapijakis C, Koronellos N, Spyridonidou S, et al (2013). Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with decreased risk for basal cell carcinoma. Arch Dermatol Res, 305, 333-9.   DOI
43 Yuan F, Zhang LS, Li HY, et al (2013). Influence of angiotensin I-converting enzyme gene polymorphism on hepatocellular carcinoma risk in China. DNA Cell Biol, 32, 268-73.   DOI   ScienceOn
44 Zhang K, Cheng D, Yi L, et al (2014). Association between angiotensin I-converting enzyme gene polymorphism and susceptibility to cancer: a meta analysis. Int J Clin Exp Pathol, 7, 6291-300.