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조현병 환자에게서 RORA 유전자 다형성과 항정신병 약물과 관련된 하지불안증후군의 연관성

Association between Antipsychotic-Related Restless Legs Syndrome and the RORA Gene Polymorphism in Schizophrenia

박영민|김린|조철현|강승걸|이헌정|윤호경|정진숙
대한조현병학회 (Korean Academy of Schizophrenia)|2013.10|대한조현병학회지 (Korean Journal of Schizophrenia Research)|제16권 제2호|pp. 93-97

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키워드

하지불안증후군·조현병·RORA·유전자 다형성·하루주기리듬.RLS · Schizophrenia · RORA · Genetic polymorphism · Circadian rhythm.
주제분류정신과학

초록

RLS는 강한 유전성을 보이는 질환이며 증상이 주기적으로 발현되는 데 생체시계가 연관이 있다고 알려져 있다. 하루주기리듬을 만들어내는 데 중요한 전사인자인 RORA가 RLS의 발생 취약성에 있어서 좋은 후보 유전자가 될 수 있겠다. 본 연구에서는 RORA 유전자의 다형성과 항정신병 약물과 연관된 RLS의 관계를 살펴보고자 190명(44명의 RLS, 146명의 non-RLS)의 조현병 환자들을 대상으로 연구하였다. 결론적으로 RORA 유전자 다형성과 항정신병약제와 관련된 RLS의 연관성을 발견하지 못하였다. 그러나 본 연구는 RORA 유전자 다형성과 항정신병약물과 관련된 RLS의 연관성을 살펴본 연구로 의의가 있으며 향후 RLS와 다른 생체시계와 연관된 추가적인 후보 유전자들에 대한 연구가 진행된다면 RLS의 유전학적 병태생리를 이해하는데 큰 도움이 될 것이다.

Abstract

Objectives : The previous studies have suggested genetic vulnerability to restless legs syndrome (RLS) development. The occurrence of antipsychotic-related RLS could also be attributable to differences in genetic susceptibility. This study aimed to investigate whether Retinoid-related orphan receptor A (RORA) gene polymorphism is associated with antipsychotic-related RLS in schizophrenia. Methods : We assessed symptoms of antipsychotic-induced RLS in 190 Korean schizophrenic patients and divided the subjects into two groups according to the International Restless Legs Syndrome Study Group diagnostic criteria : 1) subjects that met all of the criteria (n=44) and 2) the remaining subjects who were not considered to be RLS patients (n=146). Single-nucleotide polymorphism in the RORA gene was genotyped by PCR in 190 individuals. The χ2-test was conducted to compare differences between two groups. Results : The frequencies of genotype (χ2=0.066, p=0.968) of the RORA gene (rs11071547) did not differ significantly between schizophrenic patients with and without RLS. The difference of allele frequencies (χ2=0.008, p=0.927) of the RORA gene (rs 11071547) between the schizophrenic patients with and without RLS were not significant. Conclusion : These results suggest that RORA gene polymorphism does not play a major role in susceptibility to antipsychotic-related RLS in schizophrenia.

참고문헌 (51)

  1. Karroum E, "Restless-legs syndrome", Rev Neurol (Paris), 164, pp.701~721 (2008)
  2. Rasmussen J, "Restless legs syndrome and depression", Ugeskr Laeger, 173, pp.2113~2117 (2011)
  3. Kim WH, "Res-tless legs syndrome in older people: a community-based study on its prevalence and association with major depressive disorder in older Korean adults", Int J Geriatr Psychiatry, 27, pp.565~572 (2012)
  4. Winter AC, "Restless legs syndrome and risk of incident cardiovascular disease in women and men: prospective cohort study", BMJ Open, 2, pp.e000866~ (2012)
  5. Cho YW, "Epidemiology of restless legs syndrome in Korean adults", Sleep, 31, pp.219~223 (2008)
  6. Trotti LM, "Restless legs syndrome", Handb Clin Neurol, 100, pp.661~673 (2011)
  7. Giguere V, "Iso-form-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors", Genes Dev, 8, pp.538~553 (1994)
  8. Gachon F, "The mammalian circadian timing system: from gene expression to physiology", Chromosoma, 113, pp.103~112 (2004)
  9. DeBruyne JP, "CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock", Nat Neurosci, 10, pp.543~545 (2007)
  10. Guillaumond F, "Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors", J Biol Rhythms, 20, pp.391~403 (2005)
  11. Sato TK, "A functional genomics strategy reveals Rora as a component of the mammalian circadian clock", Neuron, 43, pp.527~537 (2004)
  12. Solt LA, "The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis", Future Med Chem, 3, pp.623~638 (2011)
  13. Champion D, "Growing pains: Twin family study evidence for genetic susceptibility and a genetic relationship with restless legs syndrome", Eur J Pain (2012)
  14. Desautels A, "Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q", Am J Hum Genet, 69, pp.1266~1270 (2001)
  15. Bonati MT, "Autosomal dominant restless legs syndrome maps on chromosome 14q", Brain, 126, pp.1485~1492 (2003)
  16. Chen S, "Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p", Am J Hum Genet, 74, pp.876~885 (2004)
  17. Levchenko A, "A novel autosomal dominant restless legs syndrome locus maps to chromosome 20p13", Neurology, 67, pp.900~901 (2006)
  18. Pichler I, "Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate", Am J Hum Genet, 79, pp.716~723 (2006)
  19. Kemlink D, "Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13", Neurogenetics, 9, pp.75~82 (2008)
  20. Levchenko A, "Autosomal-dominant locus for Restless Legs Syndrome in French-Canadians on chromosome 16p12.1", Mov Disord, 24, pp.40~50 (2009)
  21. Stefansson H, "A genetic risk factor for periodic limb movements in sleep", N Engl J Med, 357, pp.639~647 (2007)
  22. Winkelmann J, "Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions", Nat Genet, 39, pp.1000~1006 (2007)
  23. Schormair B, "PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome", Nat Genet, 40, pp.946~948 (2008)
  24. Kang SG, "Characteristics and clinical correlates of restless legs syndrome in schizophrenia", Prog Neuropsychopharmacol Biol Psychiatry, 31, pp.1078~1083 (2007)
  25. Kang SG, "Restless legs syndrome and periodic limb movements during sleep probably associated with olanzapine", J Psychopharmacol, 23, pp.597~601 (2009)
  26. Kang SG, "Possible association between G-protein β3 subunit C825T polymorphism and antipsychotic-induced restless legs syndrome in schizophrenia", Acta Neuropsychiatrica, 19, pp.351~356 (2007)
  27. Kang SG, "Association study between antipsychotics- induced restless legs syndrome and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in schizophrenia", Neuropsychobiology, 57, pp.49~54 (2008)
  28. Chul-Hyun Cho, "Association between Antipsychotics-Induced Restless Legs Syndrome and Tyrosine Hydroxylase Gene Polymorphism", PSYCHIATRY INVESTIGATION, 6(3), pp.211~215 (2009), 대한신경정신의학회
  29. Kang SG, "Association study between antipsychotic-induced restless legs syndrome and polymorphisms of monoamine oxidase genes in schizophrenia", Hum Psychopharmacol, 25, pp.397~403 (2010)
  30. Kang SG, "The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia", Hum Psychopharmacol, 28, pp.117~123 (2013)
  31. Walters AS, "Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome", Sleep Med, 4, pp.121~132 (2003)
  32. Soldatos CR, "The diagnostic validity of the Athens Insomnia Scale", J Psychosom Res, 55, pp.263~267 (2003)
  33. Lykke J, "Validity of the BPRS, the BDI and the BAI in dual diagnosis patients", Addict Behav, 33, pp.292~300 (2008)
  34. Michaud M, "Circadian rhythm of restless legs syndrome: relationship with biological markers", Ann Neurol, 55, pp.372~380 (2004)
  35. Odrcich M, "Chronobiological characteristics of painful diabetic neuropathy and postherpetic neuralgia: diurnal pain variation and effects of analgesic therapy", Pain, 120, pp.207~212 (2006)
  36. Baier PC, "Circadian variation in restless legs syndrome", Sleep Med, 8, pp.645~650 (2007)
  37. Akashi M, "The orphan nuclear receptor RORalpha regulates circadian transcription of the mammalian core-clock Bmal1", Nat Struct Mol Biol, 12, pp.441~448 (2005)
  38. Kamphuis W, "Circadian expression of clock genes and clock-controlled genes in the rat retina", Biochem Biophys Res Commun, 330, pp.18~26 (2005)
  39. Tosini G, "Localization of a circadian clock in mammalian photoreceptors", FASEB J, 21, pp.3866~3871 (2007)
  40. Yang X, "Nuclear receptor expression links the circadian clock to metabolism", Cell, 126, pp.801~810 (2006)
  41. Ueda HR, "A transcription factor response element for gene expression during circadian night", Nature, 418, pp.534~539 (2002)
  42. Ino H, "Immunohistochemical characterization of the orphan nuclear receptor ROR alpha in the mouse nervous system", J Histochem Cytochem, 52, pp.311~323 (2004)
  43. Boukhtouche F, "Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis", J Neurochem, 96, pp.1778~1789 (2006)
  44. Frederic F, "Enhanced endocrine response to novel environment stress and lack of corticosterone circadian rhythm in staggerer (Rora sg", sg) mutant mice, 2006, pp.83, 1525~1532
  45. Jarvis CI, "Age-related phenotypes in the staggerer mouse expand the RORalpha nuclear receptor’s role beyond the cerebellum", Mol Cell Endocrinol, 186, pp.1~5 (2002)
  46. Dzhagalov I, "Lymphocyte development and function in the absence of retinoic acid-related orphan receptor alpha", J Immunol, 173, pp.2952~2959 (2004)
  47. Kopmels B, "Evidence for a hyperexcitability state of staggerer mutant mice macrophages", J Neurochem, 58, pp.192~199 (1992)
  48. Kripke DF, "FMR1, circadian genes and depression: suggestive associations or false discovery?", J Circadian Rhythms, 11, pp.3~ (2013)
  49. Lavebratt C, "PER2 variantion is associated with depression vulnerability", Am J Med Genet B Neuropsychiatr Genet, 153, pp.570~581 (2010)
  50. Utge SJ, "Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance", PLoS One, 5, pp.e9259~ (2010)
  51. Daniel F. Kripke, "Genotyping Sleep Disorders Patients", PSYCHIATRY INVESTIGATION, 7(1), pp.36~42 (2010), 대한신경정신의학회

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