Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 6, pp 1123–1129 | Cite as

Genetic association study from North India to analyze association of CYP19A1 and CYP17A1 with polycystic ovary syndrome

  • Ratneev Kaur
  • Tajinder Kaur
  • Anupam Kaur



Polycystic ovary syndrome (PCOS) is a complex multifactorial endocrine disorder affecting approximately 5–10% of women of reproductive age. Affected women have menstrual disturbances due to anovulation, infertility, and hyperandrogenism. Ovarian androgen overproduction is the key physiopathologic feature of PCOS. A number of genes encoding major enzymes of the androgen metabolic pathways, such as HSD17B6, CYP19A1, CYP11A1, CYP17A1, and INSR, have been examined. Very few studies have been done in North India. There is an increasing prevalence of PCOS in women in Punjab and it is the leading cause of female infertility. In view of the strong evidence implicating the importance of CYP19A1 and CYP17A1 in androgen metabolic pathways, we investigated the association of rs700519, rs2414096, and rs743572 (− 34T>C) polymorphisms on susceptibility of developing PCOS, in North India.


A total of 500 subjects (women of reproductive age) including 250 PCOS cases and 250 healthy age-matched controls were included in the present study. DNA was extracted from venous blood for all samples, and association analysis for rs2414096, rs700519, and rs743572 was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Lipid profile was done using a biochemical analyzer and body mass index (BMI) was measured for all cases. Statistical analysis was performed.


Significant association of − 34T>C polymorphism of CYP17A1 was found with PCOS (p = 0.0005). BMI was statistically different between PCOS cases and controls (p = 0.000). Triglycerides were high in PCOS women. Variations of CYP19A1 were not statistically significant with PCOS.


These data suggest that − 34T>C polymorphism in CYP17A1 is associated with PCOS in North India. No polymorphism of CYP19A1 was found to be associated.


CYP17A1 CYP19A1 BMI Polycystic ovary syndrome Polymorphism Lipid profile 



We would like to thank patients from Hartej Hospital, Amritsar, for providing us blood samples for our study.

Funding information

The study was supported by UGC-UPE (non-NET) fellowship and CPEPA.

Compliance with ethical standards

This study was approved by the ethics review board of Guru Nanak Dev University, consistent with provisions of the Declaration of Helsinki. Voluntary written informed consent was obtained.


  1. 1.
    Akgul S, Derman O, Alikaşifoglu M, Aktaş D. CYP1A1 polymorphism in adolescents with polycystic ovary syndrome. Int J Gynecol Obstet. 2011;112:8–10.CrossRefGoogle Scholar
  2. 2.
    Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome society. Fertil Steril. 2004;81:19–25.Google Scholar
  3. 3.
    Dumitrescu R, Mehedintu C, Briceag I, Purcarea V, Hudita D. The polycystic ovary syndrome: an update on metabolic and hormonal mechanisms. J Med Life. 2015;8(2):142–5.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Nidhi R, Padmalatha V, Nagarathna R, Ram A. Prevalence of polycystic ovarian syndrome in Indian adolescents. J Pediatr Adolesc Gynecol. 2011;24:223–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002 Jul;26(7):883–96.CrossRefPubMedGoogle Scholar
  6. 6.
    Kaur A. Survey of obesity among various age group girls of Punjab. Int J Phys Educ Sports Health. 2016;3(2):296–9.Google Scholar
  7. 7.
    Bentley-Lewis R, Seely E, Dunaif A. Ovarian hypertension: polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2011;40(2):433–x.CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999;84(1):165–9.PubMedGoogle Scholar
  9. 9.
    Govind A, Obhrai MS, Clayton RN. Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families. J Clin Endocrinol Metab. 1999;84(1):38–43.CrossRefPubMedGoogle Scholar
  10. 10.
    Jonard S, Robert Y, Cortet-Rudelli C, Pigny P, Decanter C, Dewailly D. Ultrasound examination of polycystic ovaries: is it worth counting the follicles? Hum Reprod. 2003;18(3):598–603.CrossRefPubMedGoogle Scholar
  11. 11.
    Diao FY, Xu M, Hu Y, Li J, Xu Z, Lin M, et al. The molecular characteristics of polycystic ovary syndrome (PCOS) ovary defined by human ovary cDNA microarray. J Mol Endocrinol. 2004;33:59–72.CrossRefPubMedGoogle Scholar
  12. 12.
    Miller WL, Bose HS. Early steps in steroidogenesis: intracellular cholesterol trafficking: thematic review series: genetics of human lipid diseases. J Lipid Res. 2011;52(12):2111–35.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Manna PR, Stetson CL, Slominski AT, Pruitt K. Role of the steroidogenic acute regulatory protein in health and disease. Endocrine. 2016;51(1):7–21.CrossRefPubMedGoogle Scholar
  14. 14.
    Harada N, Ogawa H, Shozu M, Yamada K. Genetic studies to characterize the origin of the mutation in placental aromatase deficiency. Am J Hum G E N. 1992;51:666–72.Google Scholar
  15. 15.
    Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER. Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci U S A. 1993;90:11673–7.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Naessen T, Kushnir MM, Chaika A, Nosenko J, Mogilevkina I, Rockwood AL, et al. Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry. Fertil Steril. 2010;94(6):2228–33.CrossRefPubMedGoogle Scholar
  17. 17.
    Magoffin DA. Ovarian enzyme activities in women with polycystic ovary syndrome. Fertil Steril. 2006;86:S9–S11.CrossRefPubMedGoogle Scholar
  18. 18.
    Gilep AA, Sushko TA, Usanov SA. At the crossroads of steroid hormone biosynthesis: the role, substrate specificity and evolutionary development of CYP17. Biochim Biophys Acta. 2011;1814:200–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Chua AK, Azziz R, Goodarzi MO. Association study of CYP17 and HSD11B1 in polycystic ovary syndrome utilizing comprehensive gene coverage. Mol Hum Reprod. 2012;18(6):320–4.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Carey AH, Chan KL, Short F, White D, Williamson R, Franks S. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol. 1993;38(6):653–8.CrossRefGoogle Scholar
  21. 21.
    Skol AD, Scott LJ, Abecasis GR, Boehnke M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet. 2006;38:209–13.CrossRefPubMedGoogle Scholar
  22. 22.
    World Health Organisation (WHO). Appropriate body-mass index for Asian populations and its implications for policy and intervention for strategies. Lancet. 2004;363:157–63.CrossRefGoogle Scholar
  23. 23.
    Adeli K, Ogbonna G. Rapid purification of human DNA from whole blood for potential application in clinical chemistry laboratories. Clin Chem. 1990;36(2):261–4.PubMedGoogle Scholar
  24. 24.
    Wang H, Li Q, Wang T, Yang G, Wang Y, Zhang X, et al. A common polymorphism in the human aromatase gene alters the risk for polycystic ovary syndrome and modifies aromatase activity in vitro. Mol Hum Reprod. 2011;17(6):386–91.CrossRefPubMedGoogle Scholar
  25. 25.
    Jin JL, Sun J, Ge HJ, Cao YX, Wu XK, Liang FJ, et al. Association between CYP19 gene SNP rs2414096 polymorphism and polycystic ovary syndrome in Chinese women. BMC Med Genet. 2009;10:139.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Diamanti-Kandarakis E, Bartzis MI, Zapanti ED, Spina GG, Filandra FA, Tsianateli TC, et al. Polymorphism T→ C (− 34 bp) of gene CYP17 promoter in Greek patients with polycystic ovary syndrome. Fertil Steril. 1999;71(3):431–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Carey AH, Waterworth D, Patel K, White D, Little J, Novelli P, et al. Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum Mol Genet. 1994;3(10):1873–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Kahsar-Miller M, Boots L, Bartolucci A, Azziz R. Role of a CYP17 polymorphism in the regulation of circulating dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome. Fertil Steril. 2004;82:973–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Echiburú B, Pérez-Bravo F, Maliqueo M, Sánchez F, Crisosto N, Sir-Petermann T. Polymorphism T –> C (−34 base pairs) of gene CYP17 promoter in women with polycystic ovary syndrome is associated with increased body weight and insulin resistance: a preliminary study. Metabolism. 2008;57:1765–71.CrossRefPubMedGoogle Scholar
  31. 31.
    Park J, Lee E, Ramakrishna S, Cha D, Baek K. Association study for single nucleotide polymorphisms in the CYP17A1 gene and polycystic ovary syndrome. Int J Mol Med. 2008;22:249–54.PubMedGoogle Scholar
  32. 32.
    Unsal T, Konac E, Yesilkaya E, Yilmaz A, Bideci A, Ilke OH, et al. Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome. J Assist Reprod Genet. 2009;26:205–16.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Pusalkar M, Meherji P, Gokral J, Chinnaraj S, Maitra A. CYP11A1 and CYP17 promoter polymorphisms associate with hyperandrogenemia in polycystic ovary syndrome. Fertil Steril. 2009;92:653–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Mohammed MB, AL-Awadi SJ, Omran MA. Association between polycystic ovary syndrome and genetic polymorphisms of CYP 17 gene in Iraqi women. Iraqi J Biotechnol. 2015;14(2):99–110.Google Scholar
  35. 35.
    Reddy KR, Deepika MLN, Latha KP, Sagurthi SR, Lakshmanarao SS, Rahman PF, et al. Polycystic ovary syndrome: role of aromatase gene variants in south Indian women. Int J Pharm Bio Sci. 2015;6(2):1283–96.Google Scholar
  36. 36.
    Mutib MT, Hamdam FB, Salihi ARA. Effect of CYP19 gene on polycystic ovary syndrome phenotype in Iraqi women. Iraqi J Med Sci. 2015;13(3):272–8.Google Scholar
  37. 37.
    Dou Q, Tan L, Ma LY, Sun YP. The relationship between the CYP19 alleles rs727479A/C, rs700518A/G, and rs700519C/T and pregnancy outcome after assisted reproductive technology in patients with polycystic ovary syndrome in a Chinese population: a population-based study. Kaohsiung J Med Sci. 2017;33(11):558–66.CrossRefPubMedGoogle Scholar
  38. 38.
    Joshi SR. Metabolic syndrome—emerging clusters of the Indian phenotype. J Assoc Physicians India. 2003;51:445–6.PubMedGoogle Scholar
  39. 39.
    Dağ ZÖ, Dilbaz B. Impact of obesity on infertility in women. J Turk Ger Gynecol Assoc. 2015;16(2):111–7.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Sidhu S, Tatla HS. Prevalence of overweight and obesity among adult urban females of Punjab: a cross-sectional study. Anthropologist. 2002;4(2):101–3.CrossRefGoogle Scholar
  41. 41.
    Thathapudi S, Kodati V, Erukkambattu J, Katragadda A, Addepally U, Hasan Q. Anthropometric and biochemical characteristics of polycystic ovarian syndrome in South Indian women using AES-2006 criteria. Int J Endocrinol Metab. 2014;12(1):e12470.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Deepika MLN, Ranjith K, Rani VU, Ishaq M, Jahan P. Familial background of complex diseases in PCOS probands of South Indian population. Asian J Epidemiol. 2012;5(2):50–5.CrossRefGoogle Scholar
  43. 43.
    Chen J, Shen S, Tan Y, Xia D, Xia Y, Cao Y, et al. The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome. J Ovar Res. 2015;8(11):1–6.Google Scholar
  44. 44.
    Alnakash Abdulrazak H, Al-Tae e NK. Polycystic ovarian syndrome: the correlation between the LH/FSH ratio and disease manifestations. Middle East Fertil Soc J. 2007;12(1):35.Google Scholar
  45. 45.
    Haider S, Mannan N, Khan A, Qureshi MA. Influence of anthropometric measurements on abnormal gonadotropin secretion in women with polycystic ovary syndrome. J Coll Physicians Surg Pak. 2014;24(7):463–6.PubMedGoogle Scholar
  46. 46.
    Zhang XL, Zhang CW, Xu P, Liang FJ, Che YN, Xia YJ, et al. SNP rs2470152 in CYP19 is correlated to aromatase activity in Chinese polycystic ovary syndrome patients. Mol Med Rep. 2012;5:245–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Macut D, Panidis D, Glisić B, Spanos N, Petakov M, Bjekić J, et al. Lipid and lipoprotein profile in women with polycystic ovary syndrome. Can J Physiol Pharmacol. 2008;86(4):199–204.CrossRefPubMedGoogle Scholar
  48. 48.
    Techatraisak K, Wongmeerit K, Dangrat C, Wongwananuruk T, Indhavivadhana S. Measures of body adiposity and visceral adiposity index as predictors of metabolic syndrome among Thai women with PCOS. Gynecol Endocrinol. 2016;32(4):276–80.CrossRefPubMedGoogle Scholar
  49. 49.
    Unluturk U, Harmanci A, Kocaefe C, Yildiz BO. The genetic basis of the polycystic ovary syndrome: a literature review including discussion of PPAR-γ. PPAR Res. 2007;23Google Scholar
  50. 50.
    Diamanti-Kandarakis E, Piperi C, Spina J, Argyrakopoulou G, Papanastasiou L, Bergiele A, et al. Polycystic ovary syndrome: the influence of environmental and genetic factors. Hormones (Athens). 2006;5(1):17–34.CrossRefGoogle Scholar
  51. 51.
    Gharani N, Waterworth DM, Williamson R, Franks S. 5’ polymorphism of the CYP17 gene is not associated with serum testosterone levels in women with polycystic ovaries. J Clin Endocrinol Metab. 1996;81(11):4174.PubMedGoogle Scholar
  52. 52.
    Guo Y, Xiong DH, Yang TL, Guo YF, Recker RR, Deng HW. 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(16):2401–8.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Petry CJ, Ong KK, Michelmore KF, Artigas S, Wingate DL, Balen AH, et al. Association of aromatase (CYP19) gene variation with features of hyperandrogenism in two populations of young women. Hum Reprod. 2005;20(7):1837–43.CrossRefPubMedGoogle Scholar
  54. 54.
    Urbanek M, Legro RS, Driscoll DA, Azziz R, Ehrmann DA, Norman RJ, et al. Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci U S A. 1999;96(15):8573–8.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Söderlund D, Canto P, Carranza-Lira S, Méndez JP. No evidence of mutations in the P450 aromatase gene in patients with polycystic ovary syndrome. Hum Reprod. 2005;20(4):965–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Xita N, Lazaros L, Georgiou I, Tsatsoulis A. CYP19 gene: a genetic modifier of polycystic ovary syndrome phenotype. Fertil Steril. 2010;94(1):250–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Human GeneticsGuru Nanak Dev UniversityAmritsarIndia
  2. 2.Hartej HospitalAmritsarIndia

Personalised recommendations