Advertisement

Molecular Biology Reports

, Volume 39, Issue 3, pp 2313–2319 | Cite as

A common variant in the adiponectin gene and polycystic ovary syndrome risk

  • Fariba Ranjzad
  • Touraj Mahmoudi
  • Atena Irani Shemirani
  • Aidin Mahban
  • Abdolrahim Nikzamir
  • Mohsen Vahedi
  • Mahnaz Ashrafi
  • Hamid Gourabi
Article

Abstract

In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with “TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.

Keywords

Adiponectin gene PCR-RFLP Polycystic ovary syndrome 

Notes

Acknowledgments

The authors thank all patients and healthy blood donors for providing blood samples. This work was supported by a grant from the Royan Institute.

References

  1. 1.
    Legro RS (1995) The genetics of polycystic ovary syndrome. Am J Med 98:9s–16sPubMedCrossRefGoogle Scholar
  2. 2.
    Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800PubMedCrossRefGoogle Scholar
  3. 3.
    Margolin E, Zhornitzki T, Kopernik G, Kogan S, Schattner A, Knobler H (2005) Polycystic ovary syndrome in post-menopausal women—marker of the metabolic syndrome. Maturitas 50:331–336PubMedCrossRefGoogle Scholar
  4. 4.
    Xita N, Georgiou I, Chatzikyriakidou A, Vounatsou M, Papassotiriou GP, Papassotiriou I, Tsatsoulis A (2005) Effect of adiponectin gene polymorphisms on circulating adiponectin and insulin resistance indexes in women with polycystic ovary syndrome. Clin Chem 51:416–423PubMedCrossRefGoogle Scholar
  5. 5.
    Mukherjee S, Shaikh N, Khavale S, Shinde G, Meherji P, Shah N, Maitra A (2009) Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome. Eur J Endocrinol 160:855–862PubMedCrossRefGoogle Scholar
  6. 6.
    Siegel S, Futterweit W, Daries TF, Concepcion ES, Greenberg DA, Villanueva R, Tomer Y (2002) A C/T single nucleotide polymorphism at the tyrosin kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome. Fertil Steril 78:1240–1243PubMedCrossRefGoogle Scholar
  7. 7.
    Lee EJ, Yoo KJ, Kim SJ, Lee SH, Chan KY, Baek KH (2006) Single nucleotide polymorphism in exon 17 of the insulin receptor gene is not associated with polycystic ovary syndrome in a Korean population. Fertil Steril 86:380–384PubMedCrossRefGoogle Scholar
  8. 8.
    Panidis D, Kourtis A, Kukuvitis A, Farmakiotis D, Xita N, Georgiou I, Tsatsoulis A (2004) Association of the T45G polymorphism in exon 2 of the adiponectin gene with polycystic ovary syndrome: role of ∆4 androstenedione. Hum Reprod 19:1728–1733PubMedCrossRefGoogle Scholar
  9. 9.
    San Millan JL, Corton M, Villuendas G, Sancho J, Peral B, Escobar-Morreale HF (2004) Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab 89:2640–2646PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang N, Shi YH, Hao CF, Gu HF, Li Y, Zhao YR, Wang LC, Chen ZJ (2008) Association of C45G15G (T/G) and C276 (G/T) polymorphisms in the ADIPOQ gene with polycystic ovary syndrome among Han Chinese women. Eur J Endocrinol 158:255–260PubMedCrossRefGoogle Scholar
  11. 11.
    Demirci H, Yilmaz M, Ergun MA, Yurtcu E, Bukan N, Ayvaz G (2010) Frequency of adiponectin gene polymorphisms in polycystic ovary syndrome and the association with serum adiponectin, androgen levels, insulin resistance and clinical parameters. Gynecol Endocrinol 26:348–535PubMedCrossRefGoogle Scholar
  12. 12.
    Gedik O, Zileli MS (1977) Effects of hypocalcemia and theophylline on glucose tolerance and insulin release in human beings. Diabetes 26:813–819PubMedGoogle Scholar
  13. 13.
    Sun G, Vasdev S, Martin GR, Gadag V, Zhang H (2005) Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and β-cell function in the Newfoundland population. Diabetes 54:3336–3339PubMedCrossRefGoogle Scholar
  14. 14.
    Panidis D, Balaris C, Farmakiotis D, Rousso D, Kourtis A, Balaris V, Katsikis I, Zournatzi V, Diamanti-Kandarakis E (2005) Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome. Clin Chem 51:1691–1697PubMedCrossRefGoogle Scholar
  15. 15.
    Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, Kimmig R, Mann K, Janssen OE (2006) Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocr Diab 114:577–583CrossRefGoogle Scholar
  16. 16.
    Mahmoudi T, Gourabi H, Ashrafi M, Yazdi RS, Ezabadi Z (2010) Calciotropic hormones, insulin resistance and the polycystic ovary syndrome. Fertil Steril 93:1208–1214PubMedCrossRefGoogle Scholar
  17. 17.
    Kanzawa M, Sugimoto T, Kobayashi T, Kobayashi A, Chihara K (1999) Parathyroid hormone gene polymorphisms in primary hyperparathyroidism. Clin Endocrinol 50:583–588CrossRefGoogle Scholar
  18. 18.
    Gohda T, Shou I, Fukui M, Funabiki K, Horikoshi S, Shirato I, Tomino Y (2002) Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients. Am J Kidney Dis 39:1255–12560PubMedCrossRefGoogle Scholar
  19. 19.
    Mahmoudi T, Karimi Kh, Mohebbi SR, Fatemi SR, Zali MR (2010) Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer. Mol Biol Rep. doi: 10.1007/s11033-010-0613-1
  20. 20.
    Ates O, Dolek B, Dalyan L, Musellim B, Ongen G, Topal-Sarikaya A (2011) The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis. Mol Biol Rep 38:2633–2636PubMedCrossRefGoogle Scholar
  21. 21.
    Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A (2004) Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150:323–328PubMedCrossRefGoogle Scholar
  22. 22.
    Oh JY, Barrett-Connor E (2002) Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo study. Metabolism 51:356–359PubMedCrossRefGoogle Scholar
  23. 23.
    Ranjzad F, Mahban A, Irani Shemirani A, Mahmoudi T, Vahedi M, Nikzamir A, Zali MR (2010) Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet 28:225–232PubMedCrossRefGoogle Scholar
  24. 24.
    Zofkova II, Zajickova K, Hill M (2003) Serum parathyroid hormone levels are associated with FokI polymorphism of the vitamin D receptor gene in untreated postmenopausal women. Eur J Intern Med 14:232–236PubMedCrossRefGoogle Scholar
  25. 25.
    Baroncelli GI, Bereket A, El Kholy M, Audi L, Cesur Y, Ozkan B, Rashad M, Fernandez-Cancio M, Weisman Y, Saggese G, Hochberg Z (2008) Rickets in the Middle East: role of environment and genetic predisposition. J Clin Endocrinol Metab 93:1743–1750PubMedCrossRefGoogle Scholar
  26. 26.
    Mahmoudi T (2009) Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril 92:1381–1383PubMedCrossRefGoogle Scholar
  27. 27.
    Zawadski JK, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GE, Hershman SM (eds) Polycystic ovary syndrome. Current issues in endocrinology and metabolism. Blackwell, Boston, pp 377–384Google Scholar
  28. 28.
    Thomas GN, Tomlinson B, Chan JC, Lee ZS, Cockran CS, Critchley JA (2000) An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome. Am J Hypertens 13:745–752PubMedCrossRefGoogle Scholar
  29. 29.
    Mullersman JE, Shields JJ, Saha BK (1992) Characterization of two novel polymorphisms at the human parathyroid hormone gene locus. Hum Genet 88:589–592PubMedCrossRefGoogle Scholar
  30. 30.
    Ye WZ, Reis AF, Velho G (2000) Identification of a novel Tru9I polymorphism in the human vitamin D receptor gene. J Hum Genet 45:56–57PubMedCrossRefGoogle Scholar
  31. 31.
    Escobar-Morreale HF, Luque-Ramirez M, San Millan JL (2005) The molecular genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev 26:251–282PubMedCrossRefGoogle Scholar
  32. 32.
    Yang WS, Tsou PL, Lee WJ, Tseng DL, Chen CL, Peng CC, Lee KC, Chen MJ, Huang CJ, Tai TY, Chuang LM (2003) Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity. J Mol Med 81:428–434PubMedCrossRefGoogle Scholar
  33. 33.
    Heid IM, Wagner SA, Gohlke H, Iglseder B, Muller JC, Cip P, Ladurner G, Reiter R, Stadlmayr A, Mackevics V, Illig T, Kronenberg F, Paulweber B (2006) Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians. Diabetes 55:375–384PubMedCrossRefGoogle Scholar
  34. 34.
    Kaklamani VG, Sadim M, His A, Offit K, Oddoxu C, Ostrer H, Ahsan H, Pasche B, Mantzoros C (2008) Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. Cancer Res 68:3178–3184PubMedCrossRefGoogle Scholar
  35. 35.
    Fredriksson J, Carlsson E, Orho-Melander M, Groop L, Ridderstrale M (2006) A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects. Int J Obes 30:226–232CrossRefGoogle Scholar
  36. 36.
    Hanis CL, Bertin TK (1990) Identification of an insulin receptor exon 8 NsiI polymorphism using the polymerase chain reaction. Nucleic Acids Res 18:5923PubMedCrossRefGoogle Scholar
  37. 37.
    Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287PubMedCrossRefGoogle Scholar
  38. 38.
    Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29:306–309PubMedCrossRefGoogle Scholar
  39. 39.
    Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Fariba Ranjzad
    • 1
  • Touraj Mahmoudi
    • 2
  • Atena Irani Shemirani
    • 1
  • Aidin Mahban
    • 1
  • Abdolrahim Nikzamir
    • 3
  • Mohsen Vahedi
    • 4
  • Mahnaz Ashrafi
    • 5
  • Hamid Gourabi
    • 2
  1. 1.Research Center for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of GeneticsReproductive Biomedicine Research Center, Royan InstituteTehranIran
  3. 3.Department of Biochemistry, Faculty of MedicineAhwaz Jondi Shapour University of Medical SciencesAhwazIran
  4. 4.Department of Epidemiology and Biostatistics, School of Public HealthTehran University of Medical SciencesTehranIran
  5. 5.Department of Endocrinology and Female InfertilityReproductive Biomedicine Research Center, Royan InstituteTehranIran

Personalised recommendations