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Investigation of hormone receptor genes in migraine

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Abstract

Migraine is a common neurological condition with a complex mode of inheritance. Steroid hormones have long been implicated in migraine, although their role remains unclear. Our investigation considered that genes involved in hormonal pathways may play a role in migraine susceptibility. We therefore investigated the androgen receptor (AR) CAG repeat, and the progesterone receptor (PR) PROGINS insert by cross-sectional association analysis. The results showed no association with the AR CAG repeat in our study group of 275 migraineurs and 275 unrelated controls. Results of the PR PROGINS analysis showed a significant difference in the same cohort, and in an independent follow-up study population of 300 migraineurs and 300 unrelated controls. Analysis of the genotypic risk groups of both populations together indicated that individuals who carried the PROGINS insert were 1.8 times more likely to suffer migraine. Interaction analysis of the PROGINS variant with our previously reported associated ESR1 594A variant showed that individuals who possessed at least one copy of both risk alleles were 3.2 times more likely to suffer migraine. Hence, variants of these steroid hormone receptor genes appear to act synergistically to increase the risk of migraine by a factor of three.

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References

  1. Rasmussen BK (1999) Epidemiology and socio-economic impact of headache. Cephalalgia 19 [Suppl] 25:20–23

  2. Ducros A, Tournier-Lasserve E, Bousser MG (2002) The genetics of migraine. Lancet Neurol 1:285–293

    Article  Google Scholar 

  3. Headache classification committee for the International Headache Society (2004) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain, 2nd edn. Cephalgia 24 [Suppl 1]:1–60

  4. Headache classification committee for the International Headache Society (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain, 1st edn. Cephalgia 8 [Suppl 7]:1–96

  5. Nyholt DR, Gillespie NG, Heath AC, et al (2004) Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities. Genet Epidemiol 26:231–244

    Article  Google Scholar 

  6. Lea RA, Dohy A, Jordan K, et al (2000) Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraine. Neurogenetics 3:35–40

    Google Scholar 

  7. Peroutka SJ (2002) Sympathetic look at genetic basis of migraine. Headache 42:378–381

    Article  Google Scholar 

  8. Couturier EG, Bomhof MA, Neven AK, et al (2003) Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment. Cephalalgia 23:302–308

    Article  Google Scholar 

  9. MacGregor EA, Chia H, Vohrah RC, et al (1990) Migraine and menstruation: a pilot study. Cephalalgia 10:305–310

    Article  Google Scholar 

  10. MacGregor EA (1996) “Menstrual” migraine: towards a definition. Cephalalgia 16:11–21

    Article  CAS  PubMed  Google Scholar 

  11. Silberstein SD, Merriam GR (2000) Physiology of the menstrual cycle. Cephalalgia 20:148–154

    Article  Google Scholar 

  12. Epstein MT, Hockaday JM, Hockaday TD (1975) Migraine and reporoductive hormones throughout the menstrual cycle. Lancet 1:543–548

    Article  Google Scholar 

  13. Colson NJ, Lea RA, Quinlan S, et al (2004) The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups. Neurogenetics 5:129–133

    Article  Google Scholar 

  14. National Centre for Biotechnology Information,http://www.ncbi.nlm.nih.gov/

  15. Sleddens HF, Oostra BA, Brinkmann AO, et al (1992) Trinucleotide repeat polymorphism in the androgen receptor gene (AR). Nucleic Acids Res 20:1427

    Google Scholar 

  16. Westberg L, Baghaei F, Rosmond R, et al (2001) Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women. J Clin Endocrinol Metab 86:2562–2568

    Article  CAS  PubMed  Google Scholar 

  17. Krithivas K, Yurgalevitch SM, Mohr BA, et al (1999) Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J Endocrinol 162:137–142

    CAS  PubMed  Google Scholar 

  18. Chamberlain NL, Driver ED, Miesfeld RL (1994) The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 22:3181–3186

    CAS  PubMed  Google Scholar 

  19. Yong EL, Ghadessy F, Wang Q, et al (1998) Androgen receptor transactivation domain and control of spermatogenesis. Rev Reprod 3:141–144

    Article  Google Scholar 

  20. Zitzmann M, Brune M, Kornmann B, et al (2001) The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity. J Clin Endocrinol Metab 86:4867–4873

    Article  Google Scholar 

  21. Bouchard P (1999) Progesterone and the progesterone receptor. J Reprod Med 44:153–157

    Google Scholar 

  22. Bethea CL, Lu NZ, Gundlah C, et al (2002) Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol 23:41–100

    Article  Google Scholar 

  23. Cenni B, Picard D (1999) Ligand-independent activation of steroid receptors: new roles for old players. Trends Endocrinol Metab 10:41–46

    Article  Google Scholar 

  24. Rowe SM, Coughlan SJ, McKenna NJ, et al (1995) Ovarian carcinoma-associated Taq I restriction fragment length polymorphism in intron G of the progesterone receptor gene is due to an Alu sequence insertion. Cancer Res 55:2743–2745

    Google Scholar 

  25. Tong D, Fabjani G, Heinze G, et al (2001) Analysis of the human progesterone receptor gene polymorphism progins in Austrian ovarian carcinoma patients. Int J Cancer 95:394–397

    Article  Google Scholar 

  26. Runnebaum IB, Wang-Gohrke S, Vesprini D, et al (2001) Progesterone receptor variant increases ovarian cancer risk in BRCA 1 and BRCA 2 mutation carriers who were never exposed to oral contraceptives. Pharmacogenetics 11:635–638

    Article  Google Scholar 

  27. Donaldson CJ, Crapanzano JP, Watson JC, et al (2002) PROGINS Alu insertion and human genomic diversity. Mutat Res 501:137–141

    Google Scholar 

  28. Lea RA, Curtain RP, Hutchins C, et al (2001) Investigation of the CACNA 1A gene as a candidate for typical migraine susceptibility. Am J Med Genet 105:707–712

    Article  Google Scholar 

  29. Johnson MP, Lea RA, Curtain RP, et al (2003) An investigation of the 5-HT2C receptor gene as a migraine candidate gene. Am J Med Genet 117B:86–89

    Article  Google Scholar 

  30. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    CAS  PubMed  Google Scholar 

  31. Lancaster JM, Berchuck A, Carney ME, et al (1998) Progesterone receptor gene polymorphism and risk for breast and ovarian cancer. Br J Cancer 78:277

    Google Scholar 

  32. Sham P, Curtis D (1995) Monte Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann Hum Genet 59:97–105

    PubMed  Google Scholar 

  33. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    Google Scholar 

  34. Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872

    Article  Google Scholar 

  35. Schumacher M (1990) Rapid membrane effects of steroid hormones: an emerging concept in neuroendocrinology. Trends Neurosci 13:359–362

    Article  Google Scholar 

  36. Tan RS, Pu SJ, Culberson JW (2004) Role of androgens in mild cognitive impairment and possible interventions during andropause. Med Hypotheses 62:14–18

    Article  Google Scholar 

  37. Lu NZ, Bethea CL (2002) Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys. Neuropsychopharmacology 27:12–24

    Article  Google Scholar 

  38. Blomqvist A (2000) Sex hormones and pain: a new role for brain aromatase? J Comp Neurol 423:549–551

    Google Scholar 

  39. Kurz C, Tempfer CB, Boecskoer S, et al (2001) The PROGINS progesterone receptor gene polymorphism and idiopathic recurrent miscarriage. J Soc Gynecol Investig 8:295–298

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia and Griffith University. Dr Rod Lea is supported by an NHMRC C.J. Martin Fellowship. Experiments comply with the current laws in Australia.

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Authors and Affiliations

  1. Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia

    Natalie J. Colson, Rod A. Lea, Sharon Quinlan & Lyn R. Griffiths

  2. Institute of Molecular Systematics, School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand

    Rod A. Lea

  3. Queensland Clinical Genetics Service, Royal Children’s Hospital, Brisbane, Queensland, Australia

    John MacMillan

Authors
  1. Natalie J. Colson
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  2. Rod A. Lea
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  3. Sharon Quinlan
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  4. John MacMillan
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  5. Lyn R. Griffiths
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Correspondence to Lyn R. Griffiths.

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Colson, N.J., Lea, R.A., Quinlan, S. et al. Investigation of hormone receptor genes in migraine. Neurogenetics 6, 17–23 (2005). https://doi.org/10.1007/s10048-004-0205-0

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  • DOI: https://doi.org/10.1007/s10048-004-0205-0

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