Cyclin D1 G870A polymorphism: Association with uterine leiomyoma risk and in silico analysis

Salimi,Saeedeh; Shahrakipour,Mahnaz; Hajizadeh,Azam; Mokhtari,Mojgan; Mousavi,Mahdieh; Teimoori,Batool; Yaghmaei,Minoo

doi:10.3892/br.2016.830

Cyclin D1 G870A polymorphism: Association with uterine leiomyoma risk and in silico analysis

Authors:
- Saeedeh Salimi
- Mahnaz Shahrakipour
- Azam Hajizadeh
- Mojgan Mokhtari
- Mahdieh Mousavi
- Batool Teimoori
- Minoo Yaghmaei
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Affiliations: Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Sistan and Baluchestan 9816743175, Iran, Department of Biostatistics and Epidemiology, School of Public Health, Zahedan University of Medical Sciences, Zahedan, Sistan and Baluchestan 9816743175, Iran, Department of Obstetrics and Gynecology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Sistan and Baluchestan 9816743175, Iran, Department of Biology, Faculty of Science, University of Zabol, Zabol, Sistan and Baluchestan 9861335856, Iran, Department of Obstetrics and Gynecology, School of Medicine, Shahid Beheshty University of Medical Sciences, Tehran 1985717413, Iran
Published online on: December 21, 2016 https://doi.org/10.3892/br.2016.830
Pages: 237-241

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Abstract

Uterine leiomyoma (UL) is the most common benign tumor causing considerable morbidity during the reproductive years in women. Cyclin D1 (CCND1) is a cell cycle regulatory protein that is required for the G1 phase, and increased expression levels of this protein may affect tumorigenesis. The present study aimed to assess the possible effect of the CCND1 G870A polymorphism on UL susceptibility. A total of 154 women with UL and 197 healthy women who were age‑, body mass index (BMI)‑ and ethnicity‑matched were genotyped for the CCND1 G870A (rs9344) polymorphism using the polymerase chain reaction‑restriction fragment length polymorphism method. The effects of G870A transition on the structure of mRNA and proteins of CCND1 was evaluated using bioinformatics tools. The frequency of the CCND1 870AA genotype was significantly higher in women with UL compared with the control subjects, and the risk of UL was 1.4‑fold higher in women with the AA genotype when compared with the GG genotype before and after adjusting for age, BMI, and ethnicity [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1‑2 (P=0.02)]. The frequency of CCND1 870GA genotype was not significantly different between the two groups. The frequency of the CCND1 870A allele was significantly higher in the women with UL when compared with the control subjects (57 vs. 48%; P=0.02). The in silico analysis revealed that the G870A transition may fundamentally alter the structure of the CCND1‑mRNA. Thus, the CCND1 870AA genotype was associated with UL susceptibility in a sample of women from the southeast of Iran.

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1	Stewart EA, Friedman AJ, Peck K and Nowak RA: Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle. J Clin Endocrinol Metab. 79:900–906. 1994. View Article : Google Scholar : PubMed/NCBI
2	Barbarisi A, Petillo O, Di Lieto A, Melone MA, Margarucci S, Cannas M and Peluso G: 17-beta estradiol elicits an autocrine leiomyoma cell proliferation: Evidence for a stimulation of protein kinase-dependent pathway. J Cell Physiol. 186:414–424. 2001. View Article : Google Scholar : PubMed/NCBI
3	Jeon YT, Kim JW, Park NH, Song YS, Kang SB and Lee HP: DNA repair gene XRCC1 Arg399Gln polymorphism is associated with increased risk of uterine leiomyoma. Hum Reprod. 20:1586–1589. 2005. View Article : Google Scholar : PubMed/NCBI
4	Gittenberger-de Groot AC, DeRuiter MC, Bergwerff M and Poelmann RE: Smooth muscle cell origin and its relation to heterogeneity in development and disease. Arterioscler Thromb Vasc Biol. 19:1589–1594. 1999. View Article : Google Scholar
5	Medikare V, Kandukuri LR, Ananthapur V, Deenadayal M and Nallari P: The genetic bases of uterine fibroids; a review. J Reprod Infertil. 12:181–191. 2011.PubMed/NCBI
6	Vikhlyaeva EM, Khodzhaeva ZS and Fantschenko ND: Familial predisposition to uterine leiomyomas. Int J Gynaecol Obstet. 51:127–131. 1995. View Article : Google Scholar : PubMed/NCBI
7	Galderisi U, Jori FP and Giordano A: Cell cycle regulation and neural differentiation. Oncogene. 22:5208–5219. 2003. View Article : Google Scholar : PubMed/NCBI
8	Sherr CJ: Cancer cell cycles. Science. 274:1672–1677. 1996. View Article : Google Scholar : PubMed/NCBI
9	Shevra CR, Ghosh A and Kumar M: Cyclin D1 and Ki-67 expression in normal, hyperplastic and neoplastic endometrium. J Postgrad Med. 61:15–20. 2015. View Article : Google Scholar : PubMed/NCBI
10	Bae DS, Cho SB, Kim YJ, Whang JD, Song SY, Park CS, Kim DS and Lee JH: Aberrant expression of cyclin D1 is associated with poor prognosis in early stage cervical cancer of the uterus. Gynecol Oncol. 81:341–347. 2001. View Article : Google Scholar : PubMed/NCBI
11	Ayed A and Adesina A: Prognostic significance of cyclin D1 expression in resected stage I, II non-small cell lung cancer in Arabs. Interact Cardiovasc Thorac Surg. 5:47–51. 2006. View Article : Google Scholar : PubMed/NCBI
12	Abramson VG, Troxel AB, Feldman M, Mies C, Wang Y, Sherman L, McNally S, Diehl A and Demichele A: Cyclin D1b in human breast carcinoma and coexpression with cyclin D1a is associated with poor outcome. Anticancer Res. 30:1279–1285. 2010.PubMed/NCBI
13	Betticher DC, Thatcher N, Altermatt HJ, Hoban P, Ryder WD and Heighway J: Alternate splicing produces a novel cyclin D1 transcript. Oncogene. 11:1005–1011. 1995.PubMed/NCBI
14	Han SS, No JH, Jeon YT, Kim JW, Park NH, Song YS, Kang SB and Lee HP: Association of cyclin D1 G870A polymorphism with uterine leiomyoma in women whose body mass index values are above 25 kg/m2. Hum Reprod. 23:525–529. 2008. View Article : Google Scholar : PubMed/NCBI
15	Sabarinathan R, Tafer H, Seemann SE, Hofacker IL, Stadler PF and Gorodkin J: The RNAsnp web server: Predicting SNP effects on local RNA secondary structure. Nucleic Acids Res. 41:W475–W479. 2013. View Article : Google Scholar : PubMed/NCBI
16	Mallya SM and Arnold A: Cyclin D1 in parathyroid disease. Front Biosci. 5:D367–D371. 2000. View Article : Google Scholar : PubMed/NCBI
17	Catalano S, Giordano C, Rizza P, Gu G, Barone I, Bonofiglio D, Giordano F, Malivindi R, Gaccione D, Lanzino M, et al: Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation. J Cell Physiol. 218:490–500. 2009. View Article : Google Scholar : PubMed/NCBI
18	Li HY, Xu Q, Zhu T, Zhou JH, Deng DR, Wang SX, Lu YP and Ma D: Expression and clinical significance of Pin1 and Cyclin D1 in cervical cancer cell lines and cervical epithelial tissues. Ai Zheng. 25:367–372. 2006.(In Chinese). PubMed/NCBI
19	Goumenou AG, Matalliotakis IM, Tzardi M, Fragouli IG, Mahutte NG and Arici A: p16, retinoblastoma (pRb), and cyclin D1 protein expression in human endometriotic and adenomyotic lesions. Fertil Steril 85 (Suppl 1). 1204–1207. 2006. View Article : Google Scholar
20	Kovács KA, Oszter A, Göcze PM, Környei JL and Szabó I: Comparative analysis of cyclin D1 and oestrogen receptor (alpha and beta) levels in human leiomyoma and adjacent myometrium. Mol Hum Reprod. 7:1085–1091. 2001. View Article : Google Scholar : PubMed/NCBI
21	Velez AM Abreu and Howard MS: Tumor-suppressor Genes, Cell Cycle Regulatory Checkpoints, and the Skin. N Am J Med Sci. 7:176–188. 2015. View Article : Google Scholar : PubMed/NCBI
22	Dai X, Zhang X, Wang B, Wang C, Jiang J and Wu C: Association Between Polymorphism rs678653 in Human Cyclin D1 Gene (CCND1) and Susceptibility to Cancer: A Meta-Analysis. Med Sci Monit. 22:863–874. 2016. View Article : Google Scholar : PubMed/NCBI
23	Yang M, Zhu H, Hu T, Liu S and Wang H: Association of CCND1 gene polymorphism with cervical cancer susceptibility in Caucasian population: A meta-analysis. Int J Clin Exp Med. 8:12983–12988. 2015.PubMed/NCBI
24	Shen LX, Basilion JP and Stanton VP Jr: Single-nucleotide polymorphisms can cause different structural folds of mRNA. Proc Natl Acad Sci USA. 96:7871–7876. 1999. View Article : Google Scholar : PubMed/NCBI