Skip to main content

Advertisement

SpringerLink
Log in

Association of IL-1β, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Background

Polycystic ovary syndrome (PCOS), a highly prevalent endocrinopathy is currently being designated as chronic low grade inflammatory state. IL-1β, IL-1Ra and FABP1 are critical mediators of inflammatory processes and are speculated to play a role in the pathogenesis of PCOS. The aim of this study was to study the association of IL-β, IL-1Ra and FABP1 gene polymorphisms with PCOS and related metabolic features.

Subjects

95 PCOS and 45 age matched healthy control subjects were enrolled in this study.

Methods

Polymorphism in genes IL-1β, IL-1Ra and FABP1 was studied by PCR, PCR–RFLP and sequencing methods, respectively. Hormonal and lipid profiles were evaluated for all the subjects.

Results

Hormonal and lipid profiles showed significant differences between PCOS and control subjects. Allele and genotype frequencies of IL-1β, IL-1Ra and FABP1 gene polymorphisms did not vary between the control and PCOS group. However, T allele of C[-511]T variant of IL-1β, allele II in intron 2 of IL-1Ra and A allele of A/G variant of FABP1 (rs2197076) showed significant association with many metabolic features associated with PCOS.

Conclusions

Polymorphism in genes encoding cytokines and proteins involved in lipid metabolism can provide insights into the genetics of the disease and may contribute to assess the associated risk of cardiovascular diseases (CVD), dyslipidemia and metabolic syndrome (MetS) associated with 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. March WA, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544–51.

    Article  PubMed  Google Scholar 

  2. Yildiz BO, et al. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012;27(10):3067–73.

    Article  PubMed  Google Scholar 

  3. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod, 2008. 23(3): p. 462-77.

  4. Herczeg Z, et al. Genetic and epigenetic factors of polycystic ovary syndrome. Orv Hetil. 2016;157(32):1275–81.

    Article  PubMed  Google Scholar 

  5. Marciniak A, et al. Cardiovascular system diseases in patients with polycystic ovary syndrome—the role of inflammation process in this pathology and possibility of early diagnosis and prevention. Ann Agric Environ Med. 2016;23(4):537–41.

    Article  PubMed  Google Scholar 

  6. Luque-Ramirez M, Escobar-Morreale HF. Polycystic ovary syndrome as a paradigm for prehypertension, prediabetes, and preobesity. Curr Hypertens Rep. 2014;16(12):500.

    Article  PubMed  Google Scholar 

  7. Yu HF, et al. Association between polycystic ovary syndrome and the risk of pregnancy complications: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2016;95(51):e4863.

    Article  CAS  Google Scholar 

  8. Lee I et al. Increased risk of disordered eating in polycystic ovary syndrome. Fertil Steril. 2017;107:796–802.

    Article  PubMed  Google Scholar 

  9. Zhao L, et al. Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis. Oncotarget. 2016;7(23):33715–21.

    PubMed  PubMed Central  Google Scholar 

  10. Bazarganipour F, et al. Psychological investigation in patients with polycystic ovary syndrome. Health Qual Life Outcomes. 2013;11:141.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012;77(4):300–5.

    Article  CAS  PubMed  Google Scholar 

  12. Shorakae S, et al. The emerging role of chronic low-grade inflammation in the pathophysiology of polycystic ovary syndrome. Semin Reprod Med. 2015;33(4):257–69.

    Article  CAS  PubMed  Google Scholar 

  13. Jatzko B, Ott J. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and meta-analysis. Fertil Steril. 2011;96(4):e158.

    Article  PubMed  Google Scholar 

  14. Papalou O, et al. White blood cells levels and PCOS: direct and indirect relationship with obesity and insulin resistance, but not with hyperandogenemia. Hormones (Athens). 2015;14(1):91–100.

    Google Scholar 

  15. Duleba AJ, Dokras A. Is PCOS an inflammatory process? Fertil Steril. 2012;97(1):7–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ebejer K, Calleja-Agius J. The role of cytokines in polycystic ovarian syndrome. Gynecol Endocrinol. 2013;29(6):536–40.

    Article  CAS  PubMed  Google Scholar 

  17. Akdis M, et al. Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2011;127(3):701–21 (e1–70).

    Article  CAS  PubMed  Google Scholar 

  18. Banerjee M, Saxena M. Interleukin-1 (IL-1) family of cytokines: role in type 2 diabetes. Clin Chim Acta. 2012;413(15–16):1163–70.

    Article  CAS  PubMed  Google Scholar 

  19. Bonetti TC, et al. Cytokine and hormonal profile in serum samples of patients undergoing controlled ovarian stimulation: interleukin-1beta predicts ongoing pregnancy. Hum Reprod. 2010;25(8):2101–6.

    Article  CAS  PubMed  Google Scholar 

  20. Prutsch N, et al. The role of interleukin-1beta in human trophoblast motility. Placenta. 2012;33(9):696–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Falomir-Lockhart LJ, et al. Interaction of enterocyte FABPs with phospholipid membranes: clues for specific physiological roles. Biochim Biophys Acta. 2011;1811(7–8):452–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs[mdash]mechanisms and therapeutic implications. Nat Rev Endocrinol. 2015;11(10):592–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Binas B, Erol E. FABPs as determinants of myocellular and hepatic fuel metabolism. Mol Cell Biochem. 2007;299(1–2):75–84.

    Article  CAS  PubMed  Google Scholar 

  24. Chmurzynska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet. 2006;47(1):39–48.

    Article  PubMed  Google Scholar 

  25. Haunerland NH, Spener F. Fatty acid-binding proteins–insights from genetic manipulations. Prog Lipid Res. 2004;43(4):328–49.

    Article  CAS  PubMed  Google Scholar 

  26. Huang H, et al. FABP1: a novel hepatic endocannabinoid and cannabinoid binding protein. Biochemistry. 2016;55(37):5243–55.

    Article  CAS  PubMed  Google Scholar 

  27. Schroeder F, et al. Fatty acid binding protein-1 (FABP1) and the human FABP1 T94A variant: roles in the endocannabinoid system and dyslipidemias. Lipids. 2016;51(6):655–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Elmes MW, et al. Fatty acid-binding proteins (FABPs) are intracellular carriers for Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD). J Biol Chem. 2015;290(14):8711–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Atshaves BP, et al. Liver fatty acid-binding protein and obesity. J Nutr Biochem. 2010;21(11):1015–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang G, et al. Recent insights into the biological functions of liver fatty acid binding protein 1. J Lipid Res. 2015;56(12):2238–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fauser Bart CJM. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25.

  32. Misra A. Ethnic-specific criteria for classification of body mass index: a perspective for Asian Indians and American diabetes association position statement. Diabetes Technol Ther. 2015;17(9):667–71.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ramachandran A. Diabetes and obesity—the Indian angle. Indian J Med Res. 2004;120(5):437–9.

    CAS  PubMed  Google Scholar 

  34. Bergman RN, et al. A better index of body adiposity. Obesity (Silver Spring). 2011;19(5):1083–9.

    Article  PubMed Central  Google Scholar 

  35. Falsetti L, et al. Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences. Gynecol Endocrinol. 2002;16(4):275–84.

    CAS  PubMed  Google Scholar 

  36. Tang Q, et al. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: developments in research and prospects for the future. Drug Discov Ther. 2015;9(6):380–5.

    Article  CAS  PubMed  Google Scholar 

  37. Saxena P, Prakash A, Nigam A. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility. J Hum Reprod Sci. 2011;4(1):20–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kahn HS. The “lipid accumulation product” performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison. BMC Cardiovasc Disord. 2005;5:26.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tong PC, et al. The usefulness of the International Diabetes Federation and the National Cholesterol Education Program’s Adult Treatment Panel III definitions of the metabolic syndrome in predicting coronary heart disease in subjects with type 2 diabetes. Diabetes Care. 2007;30(5):1206–11.

    Article  PubMed  Google Scholar 

  40. Kim JW, et al. Association of IL-18 genotype with impaired glucose regulation in Korean women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2012;161(1):51–5.

    Article  CAS  PubMed  Google Scholar 

  41. Walch K, et al. A common interleukin-6 gene promoter polymorphism influences the clinical characteristics of women with polycystic ovary syndrome. Fertil Steril. 2004;81(6):1638–41.

    Article  CAS  PubMed  Google Scholar 

  42. Kolbus A, et al. Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated with polycystic ovary syndrome. J Reprod Immunol. 2007;73(2):188–93.

    Article  CAS  PubMed  Google Scholar 

  43. Xia YH, Yao L, Zhang ZX. Correlation between IL-1beta, IL-1Ra gene polymorphism and occurrence of polycystic ovary syndrome infertility. Asian Pac J Trop Med. 2013;6(3):232–6.

    Article  CAS  PubMed  Google Scholar 

  44. Mu Y, et al. Interleukin 1 beta (IL-1beta) promoter C [-511] T polymorphism but not C [+3953] T polymorphism is associated with polycystic ovary syndrome. Endocrine. 2010;37(1):71–5.

    Article  CAS  PubMed  Google Scholar 

  45. Yang Y, et al. Genotype and haplotype determination of interleukin (IL) 1 beta (g. -511C > T and g. +3954C > T) and IL-1RN in polycystic ovary syndrome. Fertil Steril. 2010;94(1):384–6.

    Article  CAS  PubMed  Google Scholar 

  46. Achyut BR, et al. Genetic association of interleukin-1beta (-511C/T) and interleukin-1 receptor antagonist (86 bp repeat) polymorphisms with Type 2 diabetes mellitus in North Indians. Clin Chim Acta. 2007;377(1–2):163–9.

    Article  CAS  PubMed  Google Scholar 

  47. Patel R, et al. Association of neuropeptide-Y (NPY) and interleukin-1beta (IL1B), genotype-phenotype correlation and plasma lipids with Type-II diabetes. PLoS One. 2016;11(10):e0164437.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Yang Y, Qiao J, Li MZ. Correlation between interleukin-1 and the obesity of polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2012;47(1):9–13.

    PubMed  Google Scholar 

  49. Karakaxas D, et al. Genetic polymorphisms of interleukin 1beta gene and sporadic pancreatic neuroendocrine tumors susceptibility. World J Gastrointest Oncol. 2016;8(6):520–5.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wang H et al. Genetic polymorphisms of IL-18 rs1946518 and IL-1beta rs16944 are associated with prognosis and survival of acute myeloid leukemia. Inflamm Res. 2016;66:249–58.

    Article  PubMed  Google Scholar 

  51. Nozaki Y, et al. Polymorphisms of interleukin-1 beta and beta 3-adrenergic receptor in Japanese patients with nonalcoholic steatohepatitis. Alcohol Clin Exp Res. 2004;28(8 Suppl Proceedings):106S–10S.

    CAS  PubMed  Google Scholar 

  52. Cansancao IF, et al. Association of genetic polymorphisms of IL1beta -511 C > T, IL1RN VNTR 86 bp, IL6 -174 G > C, IL10 -819 C > T and TNFalpha -308 G > A, involved in symptomatic patients with dengue in Brazil. Inflamm Res. 2016;65(11):925–32.

    Article  CAS  PubMed  Google Scholar 

  53. Nascimento JX, et al. Importance of lipid accumulation product index as a marker of CVD risk in PCOS women. Lipids Health Dis. 2015;14:62.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Xiang S, et al. Lipid accumulation product is related to metabolic syndrome in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2013;121(2):115–8.

    Article  CAS  PubMed  Google Scholar 

  55. Singh Y, et al. A study of insulin resistance by HOMA-IR and its cut-off value to identify metabolic syndrome in urban Indian adolescents. J Clin Res Pediatr Endocrinol. 2013;5(4):245–51.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Ziaee A, et al. The threshold value of homeostasis model assessment for insulin resistance in Qazvin Metabolic Diseases Study (QMDS): assessment of metabolic syndrome. J Res Health Sci. 2015;15(2):94–100.

    PubMed  Google Scholar 

  57. Kolbus A, et al. A polymorphism of the interleukin 1 receptor antagonist is not associated with polycystic ovary syndrome in Caucasian women. Fertil Steril. 2006;85(2):523–5.

    Article  CAS  PubMed  Google Scholar 

  58. Di Renzo L, et al. Interleukin-1 (IL-1) receptor antagonist gene polymorphism in normal weight obese syndrome: relationship to body composition and IL-1 alpha and beta plasma levels. Pharmacol Res. 2007;55(2):131–8.

    Article  PubMed  Google Scholar 

  59. Nair RR, Khanna A, Singh K. Association of interleukin 1 receptor antagonist (IL1RN) gene polymorphism with recurrent pregnancy loss risk in the North Indian Population and a meta-analysis. Mol Biol Rep. 2014;41(9):5719–27.

    Article  CAS  PubMed  Google Scholar 

  60. Brouillette C, et al. Effect of liver fatty acid binding protein (FABP) T94A missense mutation on plasma lipoprotein responsiveness to treatment with fenofibrate. J Hum Genet. 2004;49(8):424–32.

    Article  CAS  PubMed  Google Scholar 

  61. Peng XE, et al. Two genetic variants in FABP1 and susceptibility to non-alcohol fatty liver disease in a Chinese population. Gene. 2012;500(1):54–8.

    Article  CAS  PubMed  Google Scholar 

  62. McIntosh AL, et al. Human FABP1 T94A variant impacts fatty acid metabolism and PPAR-alpha activation in cultured human female hepatocytes. Am J Physiol Gastrointest Liver Physiol. 2014;307(2):G164–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fisher E, et al. L-FABP T94A is associated with fasting triglycerides and LDL-cholesterol in women. Mol Genet Metab. 2007;91(3):278–84.

    Article  CAS  PubMed  Google Scholar 

  64. Robitaille J, et al. Plasma concentrations of apolipoprotein B are modulated by a gene–diet interaction effect between the LFABP T94A polymorphism and dietary fat intake in French-Canadian men. Mol Genet Metab. 2004;82(4):296–303.

    Article  CAS  PubMed  Google Scholar 

  65. Mansego ML, et al. Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population. PLoS One. 2012;7(3):e31853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Xue H, et al. Association of single-nucleotide polymorphisms rs2197076 and rs2241883 of FABP1 gene with polycystic ovary syndrome. J Assist Reprod Genet. 2016;33(1):75–83.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the support provided by BD Biosciences FACS Academy housed at Jamia Hamdard, New Delhi, India. We are also thankful to Ms. Meena Lakhanpal, SRF at National Institute of Pathology(NIOP), New Delhi, India for her help in sequencing experiments. We also sincerely acknowledge Department of Biotechnology, Faculty of Science, Jamia Hamdard for providing infrastructural support.

Author contributions

NR collected blood samples and clinical details of subjects, conducted the experiments, did data collection, tabulation and statistical analysis and wrote the manuscript; AN clinical coordinator of the study and analyzed the data; PS analyzed the data and reviewed the manuscript; SKJ analyzed the data and reviewed the manuscript; SW designed the study, provided set-up and research facilities, analyzed and interpreted the data. Also, SW reviewed and finalized the manuscript. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard (Hamdard University), New Delhi, 110062, India

    Nadia Rashid & Saima Wajid

  2. Department of Gynaecology and Obstetrics, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard (Hamdard University), New Delhi, 110062, India

    Aruna Nigam

  3. Department of Obstetrics and Gynaecology, Lady Hardinge Medical College and SSK Hospital, New Delhi, 110001, India

    Pikee Saxena

  4. Department of Biochemistry, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard (Hamdard University), New Delhi, 110062, India

    S. K. Jain

Authors
  1. Nadia Rashid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aruna Nigam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pikee Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. K. Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Saima Wajid
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Saima Wajid.

Ethics declarations

Funding

The study was supported by University Grants Commission (UGC) by providing fellowship to Nadia Rashid under CSIR-UGC NET JRF Scheme [23/06/2013(i)EU-V].

Conflicts of interest

No conflict of interests between the authors.

Additional information

Responsible Editor: John Di Battista.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 24 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rashid, N., Nigam, A., Saxena, P. et al. Association of IL-1β, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome. Inflamm. Res. 66, 621–636 (2017). https://doi.org/10.1007/s00011-017-1045-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-017-1045-3

Keywords

Search

Navigation