Volume 15, Issue 8 (9-2017)                   IJRM 2017, 15(8): 491-496 | Back to browse issues page


XML Persian Abstract Print


1- Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2- Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran , smkalantar@yahoo.com
3- Physiology Research Center, Department of Obstetrics and Gynecology, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran
4- Department of Internal Medicine, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract:   (209 Views)
Background: Genetic factors are believed to play an important role in the etiology of polycystic ovarian syndrome (PCOS) which is the most common endocrinological disorder of women in their reproductive age. Androgen metabolism is impaired in PCOS and, thus, CYP19 gene which is involved in this pathway can be a candidate gene. Previous studies have shown a relationship between single nucleotide polymorphism (SNP) of CYP19 in hyperandrogenism and PCOS in some racial groups.
Objective: This study was designed to elucidate the role of CYP19 gene in PCOS in Iran.
Materials and Methods: In this case-control study, 70 PCOS women and 70 non-PCOS women as normal control were selected. Following the informed consent, 5 ml blood was taken from individuals and subsequently, genomic DNA was extracted by salting out method. Furthermore, a set of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was carried out using specific primers for SNP rs.2414096 followed by enzyme digestion, with HSP92II.
Results: Genotype frequencies of SNP rs. 2414096 in PCOS women were as follows: AA (14.4%), AG (44.3%), and GG (41.4%) while in normal group, genotypes were 24.3%, 52.8%, and 22.9%, respectively. Allele frequencies in PCOS group were 49.3% for A and 50.7% for G, whereas normal group had a different percentage of A (36.4%) and G (63.6%). The calculations for both genotypic and allelic frequencies showed statistical significance difference.
Conclusion: Variants of SNP rs. 2414096 in CYP19 could play a role in the development of PCOS in Iranian women.
Full-Text [PDF 344 kb]   (94 Downloads) |   |   Full-Text (HTML)  (15 Views)  

Received: 2017/10/1 | Accepted: 2017/10/14 | Published: 2017/10/14

References
1. Zawadzki J, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Blackwell Scientific; 1995: 377-384.
2. Petry C, Ong K, Michelmore K. Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women. Hum Reprod 2005; 20: 1837-1843. [DOI:10.1093/humrep/deh900]
3. Yildiz B, Yarali H, Bayaraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 2031-2036. [DOI:10.1210/jc.2002-021499]
4. Williamson K, Gunn A, Johnson N, Milson S. The impact of ethnicity on the presentation of polycystic ovarian syndrome. Aust N Z J Obs Gynaecol 2001; 41: 202-206. [DOI:10.1111/j.1479-828X.2001.tb01210.x]
5. Gaasenbeek M, Powell B, Sovio U, Haddad L. Large-scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone. J Clin Endocrinol Metab 2004; 89: 2408-2413. [DOI:10.1210/jc.2003-031640]
6. Diamanti-Kandarakis E, Bartzis M, Zapanti E. Polymorphism T→C (34 bp) of gene CYP17 promoter in Greek patients with polycystic ovary syndrome. Fertil Steril 1999; 71: 431-435. [DOI:10.1016/S0015-0282(98)00512-3]
7. Jones M, Italiano L, Wilson S, Mullin B. Polymorphism in HSD17B6 is associated with key features of polycystic ovary syndrome. Fertil Steril 2006; 86: 1438-1446. [DOI:10.1016/j.fertnstert.2006.04.027]
8. Jin L, Zhu X, Luo Q, Qian Y. A novel SNP at exon 17 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS. Mol Hum Reprod 2006; 3: 151-155. [DOI:10.1093/molehr/gal022]
9. Gharani N, Waterworth D, Batty S. Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Hum Mol Genet 1997; 6: 397-402. [DOI:10.1093/hmg/6.3.397]
10. Bulun S, Takayama K, Suzuki T, Sasano H, Yilmaz B, Sebastian S. Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med 2004; 22: 5-9. [DOI:10.1055/s-2004-823022]
11. Dhatariya K, Nair K. Dehydroepiandrosterone: is there a role for replacement? Mayo Clin Proc 2003; 78: 1257-1273. [DOI:10.4065/78.10.1257]
12. Guo Y, Xiong D, Yang T. Polymorphisms of estrogen-biosynthesis genes CYP17 and CYP19 may influence age at menarche: a genetic association study in Caucasian females. Hum Mol Genet 2006; 15: 2401-2408. [DOI:10.1093/hmg/ddl155]
13. Bulun S, Sebastian S, Takayama K, Suzuki T, Sasano H, Shozu M. The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol 2003; 86: 219-224. [DOI:10.1016/S0960-0760(03)00359-5]
14. Meinhardt U, Mullis P. The essential role of the aromatase/p450arom. Semin Reprod Med 2002; 20: 277-283. [DOI:10.1055/s-2002-35374]
15. Sowers M, Wilson A, Kardia S, Chu J, Ferrel R. Aromatase Gene (CYP 19) Polymorphisms and Endogenous Androgen Concentrations in a Multiracial/Multiethnic, Multisite Study of Women at Midlife. Am J Med 2006; 119: 23-30. [DOI:10.1016/j.amjmed.2006.07.003]
16. Xita N, Lazaros L, Georgiou I, Tsatsoulis A. CYP19 gene: a genetic modifier of polycystic ovary syndrome phenotype. Fertil Steril 2010; 94: 250-254. [DOI:10.1016/j.fertnstert.2009.01.147]
17. Jin J, Sun J, Ge H, Cao Y. Association between CYP19 gene SNP rs2414096 Polymorphism and polycystic ovary syndrome in Chinese women. BMC Med Genet 2009; 10: 139. [DOI:10.1186/1471-2350-10-139]
18. The 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 2004; 81: 19-25. [DOI:10.1016/j.fertnstert.2003.10.004]
19. Yu Y, Sun C, Liu Y, Li Y, Wang L, Zhang W. Promoter methylation of CYP19A1 gene in Chinese polycystic ovary syndrome patients. Gynecol Obstet Invest 2013; 76: 209-213 [DOI:10.1159/000355314]
20. Xu P, Zhang XL, Xie GB, Zhang CW, Shen SM, Zhang XX, et al. The (TTTA) n polymorphism in intron 4 of CYP19 and the polycystic ovary syndrome risk in a Chinese population. Mol Biol Rep 2013; 40: 5041-5047. [DOI:10.1007/s11033-013-2605-4]
21. Zhang X, Zhang C, Xu P, Liang F. SNP rs2470152 in CYP19 is correlated to aromatase activity in Chinese polycystic ovary syndrome patients. Mol Med Rep 2012; 5: 245-249.
22. Ghasemi N, Mortazavizadeh MR, Khorasani Gerdekoohi A. Frequency of poly cystic ovary syndrome in patients with premenopausal breast cancer. Int J Reprod Biomed 2010; 8: 86-89.
23. Mehdizadeh A, Sheikhha MH, Kalantar SM, Aali BS, Ghanei A. Mutation analysis of exon1 of bone morphogenetic protein-15 gene in Iranian patients with polycystic ovarian syndrome. Int J Reprod Biomed 2016; 14: 527-532.