Study of the association of the T869C polymorphism of the transforming growth factor-β1 gene with polycystic ovary syndrome

Park,Jung‑Hyun; Li,Lan; Baek,Kwang‑Hyun

doi:10.3892/mmr.2015.3896

Study of the association of the T869C polymorphism of the transforming growth factor-β1 gene with polycystic ovary syndrome

Authors:
- Jung‑Hyun Park
- Lan Li
- Kwang‑Hyun Baek
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Affiliations: Department of Biomedical Science, CHA University, Bundang CHA Hospital, Seongnam‑Si, Gyeonggi‑Do 463‑840, Republic of Korea
Published online on: June 8, 2015 https://doi.org/10.3892/mmr.2015.3896
Pages: 4560-4565

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Abstract

Polycystic ovary syndrome (PCOS) is a common multifactorial disorder characterized by hyperandrogenism, insulin resistance and chronic oligoanovulation. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle and an imbalance of female hormones compared with normal controls. The transforming growth factor β1 (TGF‑β1) gene is one of the genes associated with obesity and type 2 diabetes, which are characteristic symptoms of PCOS. The present study, therefore, investigated the association between the T869C polymorphism of the TGF‑β1 gene, a single nucleotide polymorphism (SNP) of TGF‑β1 and PCOS. The genomic DNA from 285 patients with PCOS and 129 healthy control individuals was used in the present study. P<0.05 was considered to indicate a statistically significant difference between the groups. The present study findings suggested that the frequency of genotypes provided no significant association between the T869C polymorphism in the TGF‑β1 gene and patients with PCOS. Although the present study concluded that the T869C polymorphism in the TGF‑β1 gene is not associated with the pathogenesis of PCOS, further studies regarding the correlation between other SNPs of the TGF‑β1 gene and PCOS are required.

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1	Zadeh-Vakili A, Ramezani Tehrani F, Daneshpour MS, Zarkesh M, Saadat N and Azizi F: Genetic polymorphism of vitamin D receptor gene affects the phenotype of PCOS. Gene. 515:193–196. 2013. View Article : Google Scholar
2	Carmina E and Lobo RA: Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab. 84:1897–1899. 1999. View Article : Google Scholar : PubMed/NCBI
3	Futterweit W: Polycystic ovary syndrome: Clinical perspectives and management. Obstet Gynecol Surv. 54:403–413. 1999. View Article : Google Scholar : PubMed/NCBI
4	Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 81:19–25. 2004. View Article : Google Scholar
5	Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 19:41–47. 2004. View Article : Google Scholar
6	Qiao J and Feng HL: Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update. 17:17–33. 2011. View Article : Google Scholar
7	Tal R, Seifer DB, Shohat-Tal A, Grazi RV and Malter HE: Transforming growth factor-beta1 and its receptor soluble endoglin are altered in polycystic ovary syndrome during controlled ovarian stimulation. Fertil Steril. 100:538–543. 2013. View Article : Google Scholar : PubMed/NCBI
8	Diamanti-Kandarakis E, Kandarakis H and Legro RS: The role of genes and environment in the etiology of PCOS. Endocrine. 30:19–26. 2006. View Article : Google Scholar : PubMed/NCBI
9	Dantas WS, Gualano B, Rocha MP, Barcellos CR, dos Reis Vieira Yance V and Marcondes JA: Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue. Scientific World J. 2013:1783642013.
10	Doi SA, Towers PA, Scott CJ and Al-Shoumer KA: PCOS: an ovarian disorder that leads to dysregulation in the hypothalamic-pituitary-adrenal axis? Eur J Obstet Gynecol Reprod Biol. 118:4–16. 2005. View Article : Google Scholar
11	Ehrmann DA: Metabolic dysfunction in pcos: Relationship to obstructive sleep apnea. Steroids. 77:290–294. 2012. View Article : Google Scholar
12	Luque-Ramírez M, San Millán JL and Escobar-Morreale HF: Genomic variants in polycystic ovary syndrome. Clin Chim Acta. 366:14–26. 2006. View Article : Google Scholar
13	Urbanek M, Woodroffe A, Ewens KG, et al: Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab. 90:6623–6629. 2005. View Article : Google Scholar : PubMed/NCBI
14	Stewart DR, Dombroski BA, Urbanek M, et al: Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J Clin Endocrinol Metab. 91:4112–4117. 2006. View Article : Google Scholar : PubMed/NCBI
15	Jordan CD, Bohling SD, Charbonneau NL and Sakai LY: Fibrillins in adult human ovary and polycystic ovary syndrome: is fibrillin-3 affected in PCOS? J Histochem Cytochem. 58:903–915. 2010. View Article : Google Scholar : PubMed/NCBI
16	Letterio JJ and Roberts AB: Regulation of immune responses by TGF-beta. Annu Rev Immunol. 16:137–161. 1998. View Article : Google Scholar : PubMed/NCBI
17	Govinden R and Bhoola KD: Genealogy, expression and cellular function of transforming growth factor-beta. Pharmacol Ther. 98:257–265. 2003. View Article : Google Scholar : PubMed/NCBI
18	Taipale J, Saharinen J and Keski-Oja J: Extracellular matrix-associated transforming growth factor-beta: role in cancer cell growth and invasion. Adv Cancer Res. 75:87–134. 1998. View Article : Google Scholar : PubMed/NCBI
19	Ten Dijke P and Hill CS: New insights into TGF-beta-Smad signalling. Trends Biochem Sci. 29:265–273. 2004. View Article : Google Scholar : PubMed/NCBI
20	Bachman KE and Park BH: Duel nature of TGF-beta signaling: tumor suppressor vs. tumor promoter. Curr Opin Oncol. 17:49–54. 2005. View Article : Google Scholar
21	Moustakas A, Souchelnytskyi S and Heldin CH: Smad regulation in TGF-beta signal transduction. J Cell Sci. 114:4359–4369. 2001.
22	Massagué J: How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 1:169–178. 2000. View Article : Google Scholar
23	Shi Y and Massague J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113:685–700. 2003. View Article : Google Scholar : PubMed/NCBI
24	König HG, Kögel D, Rami A and Prehn JH: TGF-{beta}1 activates two distinct type I receptors in neurons: implications for neuronal NF-{kappa}B signaling. J Cell Biol. 168:1077–1086. 2005. View Article : Google Scholar : PubMed/NCBI
25	Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI
26	Caraci F, Battaglia G, Busceti C, et al: TGF-beta 1 protects against Abeta-neurotoxicity via the phosphatidylinositol-3-kinase pathway. Neurobiol Dis. 30:234–242. 2008. View Article : Google Scholar : PubMed/NCBI
27	Zhu Y, Culmsee C, Klumpp S and Krieglstein J: Neuroprotection by transforming growth factor-beta1 involves activation of nuclear factor-kappaB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1, 2 signaling pathways. Neuroscience. 123:897–906. 2004. View Article : Google Scholar
28	Bosco P, Ferri R, Salluzzo MG, et al: Role of the transformin g-growth-factor-beta1 gene in late-onset Alzheimer's disease: implications for the treatment. Curr Genomics. 14:147–156. 2013. View Article : Google Scholar : PubMed/NCBI
29	Sproul K, Jones MR, Mathur R, Azziz R and Goodarzi MO: Association study of four key folliculogenesis genes in polycystic ovary syndrome. BJOG. 117:756–760. 2010. View Article : Google Scholar : PubMed/NCBI
30	Welt CK, Taylor AE, Fox J, Messerlian GM, Adams JM and Schneyer AL: Follicular arrest in polycystic ovary syndrome is associated with deficient inhibin A and B biosynthesis. J Clin Endocrinol Metab. 90:5582–5587. 2005. View Article : Google Scholar : PubMed/NCBI
31	Eldar-Geva T, Spitz IM, Groome NP, Margalioth EJ and Homburg R: Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome. Hum Reprod. 16:2552–2556. 2001. View Article : Google Scholar : PubMed/NCBI
32	Hatzirodos N, Bayne RA, Irving-Rodgers HF, et al: Linkage of regulators of TGF-beta activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 25:2256–2265. 2011. View Article : Google Scholar : PubMed/NCBI
33	Akai Y, Sato H, Ozaki H, Iwano M, Dohi Y and Kanauchi M: Association of transforming growth factor-beta1 T29C polymorphism with the progression of diabetic nephropathy. Am J Kidney Dis. 38(4 Suppl 1): 182–185. 2001. View Article : Google Scholar
34	Peng Z, Zhan L, Chen S and Xu E: Association of transforming growth factor-beta1 gene C-509T and T869C polymorphisms with atherosclerotic cerebral infarction in the Chinese: a case-control study. Lipids Health Dis. 10:1002011. View Article : Google Scholar
35	Jia H, Yu L, Gao B and Ji Q: Association between the T869C polymorphism of transforming growth factor-beta 1 and diabetic nephropathy: a meta-analysis. Endocrine. 40:372–378. 2011. View Article : Google Scholar : PubMed/NCBI
36	El-Sherbini SM, Shahen SM, Mosaad YM, Abdelgawad MS and Talaat RM: Gene polymorphism of transforming growth factor-beta1 in Egyptian patients with type 2 diabetes and diabetic nephropathy. Acta Biochim Biophys Sin (Shanghai). 45:330–338. 2013. View Article : Google Scholar
37	Hou YL, Chen H, Dong ZH, et al: Clinical significance of serum transforming growth factor-beta1 in lung cancer. Cancer Epidemiol. 37:750–753. 2013. View Article : Google Scholar : PubMed/NCBI
38	Shah R, Rahaman B, Hurley CK and Posch PE: Allelic diversity in the TGFB1 regulatory region: characterization of novel functional single nucleotide polymorphisms. Hum Genet. 119:61–74. 2006. View Article : Google Scholar
39	Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ and Hutchinson IV: Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease and graft fibrosis after lung transplantation. Transplantation. 66:1014–1020. 1998. View Article : Google Scholar : PubMed/NCBI
40	Sharma K and Ziyadeh FN: The emerging role of transforming growth factor-beta in kidney diseases. Am J Physiol. 266:F829–F842. 1994.PubMed/NCBI
41	Border WA and Noble NA: Transforming growth factor beta in tissue fibrosis. N Engl J Med. 331:1286–1292. 1994. View Article : Google Scholar : PubMed/NCBI
42	Trombly DJ, Woodruff TK and Mayo KE: Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Semin Reprod Med. 27:14–23. 2009. View Article : Google Scholar : PubMed/NCBI
43	Raja-Khan N, Kunselman AR, Demers LM, Ewens KG, Spielman RS and Legro RS: A variant in the fibrillin-3 gene is associated with TGF-beta and inhibin B levels in women with polycystic ovary syndrome. Fertil Steril. 94:2916–2919. 2010. View Article : Google Scholar : PubMed/NCBI
44	Raja-Khan N, Urbanek M, Rodgers RJ and Legro RS: The role of TGF-beta in polycystic ovary syndrome. Reprod Sci. 21:20–31. 2014. View Article : Google Scholar
45	Dumesic DA and Abbott DH: Implications of polycystic ovary syndrome on oocyte development. Semin Reprod Med. 26:53–61. 2008. View Article : Google Scholar : PubMed/NCBI
46	Buraczynska M, Baranowicz-Gaszczyk I, Borowicz E and Ksiazek A: TGF-beta1 and TSC-22 gene polymorphisms and susceptibility to microvascular complications in type 2 diabetes. Nephron Physiol. 106:p69–p75. 2007. View Article : Google Scholar : PubMed/NCBI
47	Wong TY, Poon P, Chow KM, Szeto CC, Cheung MK and Li PK: Association of transforming growth factor-beta (TGF-beta) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese. Kidney Int. 63:1831–1835. 2003. View Article : Google Scholar : PubMed/NCBI
48	Li MO, Wan YY, Sanjabi S, Robertson AK and Flavell RA: Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 24:99–146. 2006. View Article : Google Scholar : PubMed/NCBI