Association of T/A polymorphism in miR-1302 binding site in CGA gene with male infertility in Isfahan population

  • Mina Jamalvandi
  • Majid Motovali-bashi
  • Farzane Amirmahani
  • Parisa Darvishi
  • Kiarash Jamshidi Goharrizi
Original Article
  • 55 Downloads

Abstract

Infertility occurs in 10–15% of couples worldwide and close to half of it is caused by male factors. One of the genes that can affect male infertility is CGA. Polymorphisms in CGA gene may affect gene expression, therefore affecting male infertility by disrupting the regulation of this gene. One of the polymorphisms is the substitution of T with A in the miR-1302 binding site in the 3′ untranslated region of the CGA gene. In this study, we explored this polymorphism in Isfahan population. In this case-control study, by the use of Tetra primer-ARMS–PCR technique, rs6631 has been investigated in 224 infertile men and 196 controls. Infertile men were recruited from Isfahan Fertility and Infertility Center. Analysis of genotype and allele frequencies indicated that the differences between case and control populations were significant for rs6631 because P = 0.00 which is above the threshold. We found a significant relationship between this polymorphism and male infertility. This study which performed for the first time in Iran suggests that polymorphism in CGA gene can affect male infertility. Also, this polymorphism has high heterozygosity, so it can be used for further studies in different populations.

Keywords

Male infertility Polymorphism CGA gene Glycoprotein hormones 

Notes

Acknowledgements

This study has been conducted in the genetics lab at the University of Isfahan (Iran) and supported financially by Departments of Research/Technology and Graduate Offices. We would like to acknowledge all the physicians and nurses of Isfahan fertility and infertility center, especially Dr. Nasr- Esfahani for clinical data.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Abhari A, Zarghami N, Shahnazi V, Barzegar A, Farzadi L, Karami H, Vahed SZ, Nouri M (2014) Significance of microRNA targeted estrogen receptor in male fertility. Iran J Basic Med Sci 17:81PubMedPubMedCentralGoogle Scholar
  2. 2.
    Hull M, Glazener C, Kelly N, Conway D, Foster P, Hinton R, Coulson C, Lambert P, Watt E, Desai K (1985) Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed) 291:1693–1697CrossRefGoogle Scholar
  3. 3.
    Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, Da Piedade I, Gunsalus KC, Stoffel M (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500CrossRefPubMedGoogle Scholar
  4. 4.
    Hotaling JM, Walsh TJ (2009) Male infertility: a risk factor for testicular cancer. Nat Rev Urol 6:550–556CrossRefPubMedGoogle Scholar
  5. 5.
    Huang C, Liu W, Ji G-X, Gu A-H, Qu J-H, Song L, Wang X-R (2012) Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population. Asian J Androl 14:691CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zhang J, Zhou D-x, Wang H-x, Tian Z (2011) An association study of SPO11 gene single nucleotide polymorphisms with idiopathic male infertility in Chinese Han population. J Assist Reprod Genet 28:731–736CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C (2007) Male infertility: role of genetic background. Reprod Biomed Online 14:734–745CrossRefPubMedGoogle Scholar
  8. 8.
    Massart A, Lissens W, Tournaye H, Stouffs K (2012) Genetic causes of spermatogenic failure. Asian J Androl 14:40CrossRefPubMedGoogle Scholar
  9. 9.
    Mirfakhraie R, Fazli H, Montazeri M, Modabber G, Salsabili N, Sayed HS, Mirzajani F, Kalantar S (2008) 7.017 Y chromosome microdeletions in Iranian infertile men. Reprod BioMed Online 16:s50–s51CrossRefGoogle Scholar
  10. 10.
    Boothby M, Ruddon R, Anderson C, McWilliams D, Boime I (1981) A single gonadotropin alpha-subunit gene in normal tissue and tumor-derived cell lines. J Biol Chem 256:5121–5127PubMedGoogle Scholar
  11. 11.
    Cahoreau C, Klett D, Combarnous Y (2015) Structure–function relationships of glycoprotein hormones and their subunits’ ancestors. Front Endocrinol 6:26CrossRefGoogle Scholar
  12. 12.
    Pierce JG, Parsons TF (1981) Glycoprotein hormones: structure and function. Annu Rev Biochem 50:465–495CrossRefPubMedGoogle Scholar
  13. 13.
    Baenziger JU, Green ED (1988) Pituitary glycoprotein hormone oligosaccharides: structure, synthesis and function of the asparagine-linked oligosaccharides on lutropin, follitropin and thyrotropin. Biochim Biophys Acta (BBA)—Rev Biomembr 947:287–306CrossRefGoogle Scholar
  14. 14.
    Li M, Ford J (1998) A comprehensive evolutionary analysis based on nucleotide and amino acid sequences of the alpha-and beta-subunits of glycoprotein hormone gene family. J Endocrinol 156:529–542CrossRefPubMedGoogle Scholar
  15. 15.
    Grossmann M, Weintraub BD, Szkudlinski MW (1997) Novel insights into the molecular mechanisms of human thyrotropin action: structural, physiological, and therapeutic implications for the glycoprotein hormone family. Endocr Rev 18:476–501CrossRefPubMedGoogle Scholar
  16. 16.
    Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (2002) Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure–function relationships. Physiol Rev 82:473–502CrossRefPubMedGoogle Scholar
  17. 17.
    Blithe DL, Richards RG, Skarulis MC (1991) Free alpha molecules from pregnancy stimulate secretion of prolactin from human decidual cells: a novel function for free alpha in pregnancy. Endocrinology 129:2257–2259CrossRefPubMedGoogle Scholar
  18. 18.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefPubMedGoogle Scholar
  19. 19.
    Sethupathy P, Collins FS (2008) MicroRNA target site polymorphisms and human disease. Trends Genet 24:489–497CrossRefPubMedGoogle Scholar
  20. 20.
    Wang G, van der Walt JM, Mayhew G, Li Y-J, Züchner S, Scott WK, Martin ER, Vance JM (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of α-synuclein. Am J Hum Genet 82:283–289CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ryan BM, Robles AI, Harris CC (2010) Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 10:389CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Miller S, Dykes D, Polesky H (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Zhang H, Liu Y, Su D, Yang Y, Bai G, Tao D, Ma Y, Zhang S (2011) A single nucleotide polymorphism in a miR-1302 binding site in CGA increases the risk of idiopathic male infertility. Fertil Steril 96:34–39 e7.CrossRefPubMedGoogle Scholar
  24. 24.
    Stark A, Bushati N, Jan CH, Kheradpour P, Hodges E, Brennecke J, Bartel DP, Cohen SM, Kellis M (2008) A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands. Genes Dev 22:8–13CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    He Z, Kokkinaki M, Pant D, Gallicano GI, Dym M (2009) Small RNA molecules in the regulation of spermatogenesis. Reproduction 137:901–911CrossRefPubMedGoogle Scholar
  26. 26.
    Yan N, Lu Y, Sun H, Qiu W, Tao D, Liu Y, Chen H, Yang Y, Zhang S, Li X (2009) Microarray profiling of microRNAs expressed in testis tissues of developing primates. J Assist Reprod Genet 26:179–186CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS, Hatzigeorgiou AG, Antonarakis SE (2007) Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet 81:405–413CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Sætrom P, Biesinger J, Li SM, Smith D, Thomas LF, Majzoub K, Rivas GE, Alluin J, Rossi JJ, Krontiris TG (2009) A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res 69:7459–7465CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Immunology, Faculty of Medical SciencesIlam University of Medical SciencesIlamIran
  2. 2.Genetic Division, Department of Biology, Faculty of SciencesUniversity of IsfahanIsfahanIran
  3. 3.Department of Plant Breeding, Yazd BranchIslamic Azad UniversityYazdIran

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