Top

Journal of Assisted Reproduction and Genetics

Published in:

01-05-2017 | Genetics

Association study of HNF1A in women with polycystic ovary syndrome

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

Published in: Journal of Assisted Reproduction and Genetics | Issue 5/2017

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.

Available only for authorised users

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

27.

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

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.

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.CrossRefPubMedPubMedCentral

Title: Association study of HNF1A in women with polycystic ovary syndrome
Authors: Yue Lv
Changfa Sun
Ye Tian
Shigang Zhao
Yuehong Bian
Lei Cheng
Mei Sun
Hong-Bin Liu
Han Zhao
Jinlong Ma
Publication date: 01-05-2017
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 5/2017
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-017-0905-7

At a glance: The STEP trials

Springer Medicine

Association study of HNF1A in women with polycystic ovary syndrome

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2017

Role of DNA methylation in imprinting disorders: an updated review

Impact of the FSHB gene -211G/T polymorphism on male gonadal function

Polar body transfer restores the developmental potential of oocytes to blastocyst stage in a case of repeated embryo fragmentation

A family study of complex chromosome rearrangement involving chromosomes 1, 8, and 11 and its reproductive consequences

In vitro fertilization for women infected by hepatitis C virus: a matched case-control study and a systematic literature review

Erratum to: The association between coenzyme Q10 concentrations in follicular fluid with embryo morphokinetics and pregnancy rate in assisted reproductive techniques