Skip to main content

Advertisement

SpringerLink
Log in

Association study of HNF1A in women with polycystic ovary syndrome

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

This study aims to ascertain whether an association exists between hepatocyte nuclear factor 1 alpha (HNF1A) and polycystic ovary syndrome (PCOS).

Methods

One thousand one hundred thirty-eight PCOS and 1125 healthy control Han Chinese women were recruited from Reproductive Hospital Affiliated to Shandong University. Serum hormone, blood lipid level, and genomic DNA were obtained from the peripheral blood for this research. Two single-nucleotide polymorphisms (SNPs)—rs2393791 and rs7305618—located in HNF1A were genotyped using the Sequenom MassARRAY system.

Results

The allele frequencies of SNP rs7305618 had significant differences between PCOS patients and controls after adjusting for age and BMI (p = 0.023). Besides, PCOS patients carrying the rs7305618 CC genotype shown a higher testosterone level than the patients with CT + TT genotypes after being adjusted by age and BMI (p = 0.019).

Conclusions

A SNP located in the HNF1A gene is associated with PCOS among Han Chinese women. This suggested that variations in HNF1A might confer risk for PCOS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9. doi:10.1210/jc.2003-032046.

    Article  CAS  PubMed  Google Scholar 

  2. Li R, Zhang Q, Yang D, Li S, Lu S, Wu X, et al. Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Hum Reprod. 2013;28(9):2562–9. doi:10.1093/humrep/det262.

    Article  PubMed  Google Scholar 

  3. Carmina E, Azziz R. Diagnosis, phenotype, and prevalence of polycystic ovary syndrome. Fertil Steril. 2006;86(Suppl 1):S7–8. doi:10.1016/j.fertnstert.2006.03.012.

    Article  PubMed  Google Scholar 

  4. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7(4):219–31. doi:10.1038/nrendo.2010.217.

    Article  CAS  PubMed  Google Scholar 

  5. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN, et al. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(1):48–53. doi:10.1210/jc.2005-1329.

    Article  CAS  PubMed  Google Scholar 

  6. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347–63. doi:10.1093/humupd/dmq001.

    Article  CAS  PubMed  Google Scholar 

  7. Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med. 2001;111(8):607–13.

    Article  CAS  PubMed  Google Scholar 

  8. Brower MA, Jones MR, Rotter JI, Krauss RM, Legro RS, Azziz R, et al. Further investigation in Europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals. J Clin Endocrinol Metab. 2015;100(1):E182–6. doi:10.1210/jc.2014-2689.

    Article  CAS  PubMed  Google Scholar 

  9. Ramos RB, Wiltgen D, Spritzer PM. Polymorphisms of TCF7L2 gene in South Brazilian women with polycystic ovary syndrome: a cross-sectional study. European journal of endocrinology / European Federation of Endocrine Societies. 2013;169(5):569–76. doi:10.1530/EJE-13-0105.

    Article  CAS  Google Scholar 

  10. Li T, Zhao H, Zhao X, Zhang B, Cui L, Shi Y, et al. Identification of YAP1 as a novel susceptibility gene for polycystic ovary syndrome. J Med Genet. 2012;49(4):254–7. doi:10.1136/jmedgenet-2011-100727.

    Article  CAS  PubMed  Google Scholar 

  11. Li C, Shi Y, You L, Wang L, Chen ZJ. Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome. Mol Hum Reprod. 2011;17(3):193–8. doi:10.1093/molehr/gaq087.

    Article  CAS  PubMed  Google Scholar 

  12. Bach I, Pontoglio M, Yaniv M. Structure of the gene encoding hepatocyte nuclear factor 1 (HNF1). Nucleic Acids Res. 1992;20(16):4199–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pontoglio M, Barra J, Hadchouel M, Doyen A, Kress C, Bach JP, et al. Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. Cell. 1996;84(4):575–85.

    Article  CAS  PubMed  Google Scholar 

  14. Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, et al. Control of pancreas and liver gene expression by HNF transcription factors. Science. 2004;303(5662):1378–81. doi:10.1126/science.1089769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shih DQ, Bussen M, Sehayek E, Ananthanarayanan M, Shneider BL, Suchy FJ, et al. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet. 2001;27(4):375–82. doi:10.1038/86871.

    Article  CAS  PubMed  Google Scholar 

  16. Wakil SM, Muiya NP, Tahir AI, Al-Najai M, Baz B, Andres E, et al. A new susceptibility locus for myocardial infarction, hypertension, type 2 diabetes mellitus, and dyslipidemia on chromosome 12q24. Dis Markers. 2014;2014:291419. doi:10.1155/2014/291419.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bellanne-Chantelot C, Carette C, Riveline JP, Valero R, Gautier JF, Larger E, et al. The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3. Diabetes. 2008;57(2):503–8. doi:10.2337/db07-0859.

    Article  CAS  PubMed  Google Scholar 

  18. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010;42(7):579–89. doi:10.1038/ng.609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Reiner AP, Barber MJ, Guan Y, Ridker PM, Lange LA, Chasman DI, et al. Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. Am J Hum Genet. 2008;82(5):1193–201. doi:10.1016/j.ajhg.2008.03.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kong M, Lee C. Genetic associations with C-reactive protein level and white blood cell count in the KARE study. International journal of immunogenetics. 2013a;40(2):120–5. doi:10.1111/j.1744-313X.2012.01141.x.

    Article  CAS  PubMed  Google Scholar 

  21. Li K, Huang T, Zheng JS, Sun J, Chen Y, Xie H, et al. Interaction between erythrocyte phospholipid fatty acids composition and variants of inflammation-related genes on type 2 diabetes. Journal of nutrigenetics and nutrigenomics. 2015;7(4–6):252–63. doi:10.1159/000381347.

    Article  Google Scholar 

  22. Chen ZJ, Zhao H, He L, Shi Y, Qin Y, Shi Y, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet. 2011;43(1):55–9. doi:10.1038/ng.732.

    Article  PubMed  Google Scholar 

  23. Shi Y, Zhao H, Shi Y, Cao Y, Yang D, Li Z, et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet. 2012;44(9):1020–5. doi:10.1038/ng.2384.

    Article  CAS  PubMed  Google Scholar 

  24. Day FR, Hinds DA, Tung JY, Stolk L, Styrkarsdottir U, Saxena R, et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun. 2015;6:8464. doi:10.1038/ncomms9464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hayes MG, Urbanek M, Ehrmann DA, Armstrong LL, Lee JY, Sisk R et al. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nature communications. 2015;6.

  26. Shende VR, Wu M, Singh AB, Dong B, Kan CF, Liu J. Reduction of circulating PCSK9 and LDL-C levels by liver-specific knockdown of HNF1alpha in normolipidemic mice. J Lipid Res. 2015;56(4):801–9. doi:10.1194/jlr.M052969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wild RA. Dyslipidemia in PCOS. Steroids. 2012;77(4):295–9. doi:10.1016/j.steroids.2011.12.002.

    Article  CAS  PubMed  Google Scholar 

  28. Wild RA, Rizzo M, Clifton S, Carmina E. Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril. 2011;95(3):1073–9. e1-11 doi:10.1016/j.fertnstert.2010.12.027.

    Article  CAS  PubMed  Google Scholar 

  29. Grimm AA, Brace CS, Wang T, Stormo GD, Imai S. A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates Crp expression. Aging Cell. 2011;10(2):305–17. doi:10.1111/j.1474-9726.2010.00667.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004;350(14):1387–97. doi:10.1056/NEJMoa032804.

    Article  CAS  PubMed  Google Scholar 

  31. Emerging Risk Factors C, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132–40. doi:10.1016/S0140-6736(09)61717-7.

    Article  Google Scholar 

  32. Kong M, Lee C. Genetic associations with C-reactive protein level and white blood cell count in the KARE study. International journal of immunogenetics. 2013b;40(2):120–5.

    Article  CAS  PubMed  Google Scholar 

  33. Mahajan A, Tabassum R, Chavali S, Dwivedi OP, Chauhan G, Ghosh S, et al. Common variants in CRP and LEPR influence high sensitivity C-reactive protein levels in North Indians. PLoS One. 2011;6(9):e24645. doi:10.1371/journal.pone.0024645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation. 2003;107(3):391–7.

    Article  PubMed  Google Scholar 

  35. Boulman N, Levy Y, Leiba R, Shachar S, Linn R, Zinder O, et al. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. J Clin Endocrinol Metab. 2004;89(5):2160–5. doi:10.1210/jc.2003-031096.

    Article  CAS  PubMed  Google Scholar 

  36. Wu Y, Zhang J, Wen Y, Wang H, Zhang M, Cianflone K. Increased acylation-stimulating protein, C-reactive protein, and lipid levels in young women with polycystic ovary syndrome. Fertil Steril. 2009;91(1):213–9. doi:10.1016/j.fertnstert.2007.11.031.

    Article  CAS  PubMed  Google Scholar 

  37. Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation. 2001;103(9):1194–7.

    Article  CAS  PubMed  Google Scholar 

  38. Dehdashtihaghighat S, Mehdizadehkashi A, Arbabi A, Pishgahroudsari M, Chaichian S. Assessment of C-reactive protein and C3 as inflammatory markers of insulin resistance in women with polycystic ovary syndrome: a case-control study. Journal of reproduction & infertility. 2013;14(4):197–201.

    CAS  Google Scholar 

  39. González F, Rote NS, Minium J, Kirwan JP. Evidence of proatherogenic inflammation in polycystic ovary syndrome. Metab Clin Exp. 2009;58(7):954–62.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We especially thank all of the participants involved in this study.

Author information

Author notes

  1. Yue Lv and Changfa Sun contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, Shandong University, No.157, Jingliu Road, Jinan, 250021, China

    Yue Lv, Changfa Sun, Ye Tian, Shigang Zhao, Yuehong Bian, Lei Cheng, Mei Sun, Hong-Bin Liu, Han Zhao & Jinlong Ma

  2. Ministry of Education, The Key Laboratory of Reproductive Endocrinology, Shandong University, Jinan, China

    Yue Lv, Changfa Sun, Ye Tian, Shigang Zhao, Yuehong Bian, Lei Cheng, Mei Sun, Hong-Bin Liu, Han Zhao & Jinlong Ma

  3. School of Biomedical Sciences, The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, The Chinese University of Hong Kong, Hong Kong SAR, China

    Yue Lv, Changfa Sun & Hong-Bin Liu

Authors
  1. Yue Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Changfa Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ye Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shigang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuehong Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hong-Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Han Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jinlong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Han Zhao or Jinlong Ma.

Ethics declarations

Each participant signed a written informed consent, and the study was approved by the Institutional Review Board of Center for Reproductive Medicine of Shandong University.

Funding

This research was supported by the National Basic Research Program of China (973 Program) (2012CB944700), the National Natural Science Foundation of China (81,430,029, 81,490,743, 31,371,453, 31,571,548), and the Young Scholars Program of Shandong University (2015WLJH54).

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

ESM 1

(DOCX 28 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lv, Y., Sun, C., Tian, Y. et al. Association study of HNF1A in women with polycystic ovary syndrome. J Assist Reprod Genet 34, 677–682 (2017). https://doi.org/10.1007/s10815-017-0905-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-017-0905-7

Keywords

Search

Navigation