Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.16.7129

Multi-Parameter Approach for Evaluation of Genomic Instability in the Polycystic Ovary Syndrome  

Sekar, Nishu (Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University)
Nair, Manju (Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University)
Francis, Glory (Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University)
Kongath, Parvathy Raj (Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University)
Babu, Sandhya (Sandhya Hospital)
Raja, Sudhakaran (Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University)
Gopalakrishnan, Abilash Valsala (Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.16, 2015 , pp. 7129-7138 More about this Journal
Abstract
Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value ($45.9^{\circ}$) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.
Keywords
Polycystic ovary syndrome; cytogenetic; dermatoglypics; buccal micronuclei analysis;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Aardema MJ, Albertini S, Arni P, et al (1998). Aneuploidy: A report of an ECETOC task force. Mutat Res, 410, 3-79.   DOI
2 Adams J, Polson DW, Abdulwahid N, et al (1985). Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet, 2, 1375-9.
3 Andrea, Dunaif, Abraham Thomas (2001). Current concepts in the polycystic ovary syndrome. Annu Rev Med, 52, 401-19.   DOI
4 Azziz R, Sanchez L, Knochenhauer ES, et al (2004). Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab, 89, 453-462.   DOI
5 Bhardwaj N, Bhardwaj P, Tewari V, Siddiqui MS (2015) . Dermatoglyphic analysis of fingertip and palmer print patterns of obese children. Int J Med Sci Public Health, 4, 946-9.
6 Bonassi S, Ugolini D, Kirsch-Volders M, et al (2005). Human population studies with cytogenetic biomarkers: review of the literature and future prospectives. Environ Mol Mutagen, 45, 258-270.   DOI
7 Cummins H and Midlo C (1961). Fingerprints, Palms and Soles. An introduction to dermatoglyphics. New York: Dover Publ, 1961.
8 Dhillon VS, Aslam M, Husain SA (2004). The contribution of genetic and epigenetic changes in granulosa cell tumors of ovarian origin. Clin Cancer Res, 10, 5537-45.   DOI
9 Diamanti-Kandarakis E, Argyrakopoulou G, Economou F, Kandaraki E, Koutsilieris M (2008). Defects in insulin signaling pathways in ovarian steroidogenesis and other tissues in polycystic ovary syndrome (PCOS). J Steroid Biochem Mol Biol, 109, 242-6.   DOI
10 Dunaif A (1997). Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev, 18, 774-800.
11 Dunaif A, Sega KR, Futterweit W, Dobrjansky A (1989). Profound peripheral insulin resistance independent of obesity in polycystic ovary syndrome. Diabetes, 38, 1165-74.   DOI
12 Elif Yesilada, Ibrahim Sahin, Hamdi Ozcan, Ibrahim Halil Yildirim, Saim Yologlu and Cagatay Taskapan (2006). Increased micronucleus frequencies in peripheral blood lymphocytes in women with polycystic ovary syndrome. Eur J Endocrinol, 154, 563-8.   DOI
13 Farquhar C (2007). Introduction and history of polycystic ovary syndrome. In: Kovacs G, Norman R, editors.Polycystic Ovary Syndrome. 2nd ed. Cambridge, UK: Cambridge University Press, 4-24.
14 Holland N, Bolognesi C, Kirsch-Volders M, et al (2008). The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: the HUMN project perspective on current status and knowledge gaps. Mutat Res, 659, 93-108.   DOI
15 Fauser B, Tarlatzis B, Rebar R, et al (2012). Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril, 97, 28-38.   DOI
16 Ferriman D, Gallwey JD (1961). Clinical assessment of body hair in women. J Clin Endocrinol Meta, 21, 1440-7.   DOI
17 Hart R. Definitions ( 2007). Prevalence and symptoms of polycystic ovaries and the polycystic ovary syndrome. In: Allahbadia GN, Agrawal R, editors. Polycystic Ovary Syndrome. Kent, UK, Anshan, Ltd,15-26.
18 Hungerford DA (1965). Leucocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Technol, 40, 333-8.   DOI
19 Lengauer C, Kinzler, KW, Vogelstein B (1998). Genetic instabilities in human cancers, Nature, 396, 643-9.   DOI
20 Lowenstein E (2006). Diagnosis and management of the dermatologic manifestations of the polycystic ovary syndrome. Dermatol Ther, 19, 210-23.   DOI
21 Majno G, Joris I (1995). Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol, 146, 3-15.
22 Meenakshi S, Balasubramanyam V, Sayee Rajangam (2006). Dermatoglyphics in amenorrhea qualitative analysis. J Obstet Gynecol India, 56, 250-4.
23 Mutalik GS, Lokhandwala VA, Anjeneyulu R (1968). Dermatoglyphical findings in primary amenorrhoea. J Obstet Gynecol India, 18, 738-43.
24 Otto PA, Otto PG (1980). The importance of a'-d ridge count in dermatoglyphic diagnosis of the ullrich-turner syndrome. Am J Med Genet, 6, 145-5.   DOI
25 Nersesyan A, Martirosyan A, Parsadanyan G, Zalinyan G (2006). Chromosomal aberrations level in peripheral blood lymphocytes of women with polycystic ovary syndrome. J BUON, 11, 477-480.
26 Nersesyan A, Chobanyan N (2010). Micronuclei and other nuclear anomalies levels in exfoliated buccal cells and DNA damage in leukocytes of patients with polycystic ovary syndrome. J BUON, 15, 337-339.
27 Nina Holland, Claudia Bolognesi, Micheline Kirsch-Volders, et al (2008). The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: The human project perspective on current status and knowledge gap. Mutat Res, 659, 93-108.   DOI
28 Poretsky L, Cataldo N, Rosenwaks Z, Guidice L (1999). The insulin-4 related ovarian regulatory system in health and disease. Endocr Rev, 20, 532-82.
29 Schaumann B, Alter M (1976). Dermatoglyphics in medical disorders. New York. Springer-Verlag.
30 Shweta Talhar S, Bharat Sontakke R, et al (2014). Dermatoglyphics and karyotype analysis in primary amenorrhoea. A J Clin Diagn Re, 12, 13-16.
31 Simpson JL (1992). Elucidating the genetics of polycystic ovary syndrome. In Dunaif, A., Givens, J.R., Haseltine, F.P. and Merriam, G.R. (eds), Polycystic ovary syndrome. Blackwell Scientific, Oxford, 59-77.
32 Stich HF, San RH, Rosin MP (1983). Adaptation of the DNArepair and micronucleus tests to human cell suspensions and exfoliated cells. Ann N Y Acad Sci, 407, 93-105.   DOI
33 Unluhizarci K, Kaltsas G, Kelestimur F (2012). Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism. Eur J Clin Invest, 42, 86-94.   DOI
34 Stich HF, Rosin MP, Vallejera MO (1984). Reduction with vitamin A and beta-carotene administration of proportion of micronucleated buccal mucosal cells in Asian betal nut and tobacco chewers. Lancet, 1, 1204-6.
35 Sundaramoorthy R, Srinivasan V, Gujar J, et al (2013). Clinical, cytogenetic and CYP1A1 exon-1 gene mutation analysis of beedi workers in vellore region, Tamil Nadu. Asian Pac J Cancer Prev, 14, 7555-60.   DOI
36 Tokmak A, Kokanali MK, Guzel AI, et al (2013). Polycystic ovary syndrome and risk of endometrial cancer, a minireview. Asian Pac J Cancer Prev, 15, 7011-14.
37 Wijeyaratne CN, Balen AH, Barth JH, Belchetz PE (2002). Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among south Asians and Caucasians: is there a difference?. Clin Endocrinol (Oxf), 57, 343-50.   DOI
38 Yadav AS , Jaggi S (2015). Buccal micronucleus cytome assay- a biomarker of genotoxicity. J Mol Biomark Diagn, 6, 236.
39 Zhao PL, Zhang QF, Yan LY, et al (2014). Functional investigation on aromatase in endometrial hyperplasia in polycystic ovary syndrome cases. Asian Pac J Cancer Prev, 15, 8975-9.   DOI