CAGn repeat of the androgen receptor is linked to proopiomelanocortin promoter methylation—relevance for craving of male alcohol-dependent patients?
详细信息 查看全文
- 作者：Marc Andre Nicolas Muschler (1) (2)
Bernd Lenz (2)
Thomas Hillemacher (1) (2)
Cornelia Kraus (3)
Johannes Kornhuber (2)
Helge Frieling (1) (2)
Stefan Bleich (1) (2) - 关键词：Alcohol dependence ; POMC ; Androgen receptor ; DNA methylation ; Bisulfite sequencing
- 刊名：Psychopharmacology
- 出版年：2014
- 出版时间：May 2014
- 年：2014
- 卷：231
- 期：10
- 页码：2059-2066
- 全文大小：
- 参考文献：1. American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders : DSM-IV-TR. Washington, DC, American Psychiatric Association.
2. Ansseau M, Besson J, Lejoyeux M, Pinto E, Landry U, Cornes M, Deckers F, Potgieter A, Ades J (2000) A French translation of the obsessive–compulsive drinking scale for craving in alcohol-dependent patients: a validation study in Belgium, France, and Switzerland. Eur Addict Res 6(2):51-6 CrossRef
3. Anton RF, Moak DH, Latham P (1995) The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res 19(1):92-9 CrossRef
4. Apter SJ, Eriksson CJ (2003) The effect of alcohol on testosterone concentrations in alcohol-preferring and non-preferring rat lines. Alcohol Clin Exp Res 27(7):1190-193 CrossRef
5. Bao AM, Fischer DF, Wu YH, Hol EM, Balesar R, Unmehopa UA, Zhou JN, Swaab DF (2006) A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry 11(6):567-76 CrossRef
6. Bleich S, Carl M, Bayerlein K, Reulbach U, Biermann T, Hillemacher T, Bonsch D, Kornhuber J (2005) Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcohol Clin Exp Res 29(3):334-36 CrossRef
7. Botbol M, Roubertoux PL, Carlier M, Trabado S, Brailly-Tabard S, Perez-Diaz F, Bonnot O, Bronsard G, Tordjman S (2011) Modulation of brain beta-endorphin concentration by the specific part of the Y chromosome in mice. PLoS One 6(3):e16704 CrossRef
8. Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A, Temper V, Razin A, Cedar H (1994) Sp1 elements protect a CpG island from de novo methylation. Nature 371(6496):435-38 CrossRef
9. Chignon JM, Jacquesy L, Mennad M, Terki A, Huttin F, Martin P, Chabannes JP (1998) Self-assessment questionnaire of alcoholic craving (ECCA Questionnaire: Behavior and Cognition in Relation to Alcohol: French translation and validation of the Obsessive-Compulsive Drinking Scale. Encéphale 24(5):426-34
10. Clark SJ, Harrison J, Paul CL, Frommer M (1994) High sensitivity mapping of methylated cytosines. Nucleic Acids Res 22(15):2990-997 CrossRef
11. Dickson J, Gowher H, Strogantsev R, Gaszner M, Hair A, Felsenfeld G, West AG (2010) VEZF1 elements mediate protection from DNA methylation. PLoS Genet 6(1):e1000804 CrossRef
12. Ehrlich S, Weiss D, Burghardt R, Infante-Duarte C, Brockhaus S, Muschler MA, Bleich S, Lehmkuhl U, Frieling H (2010) Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa. J Psychiatr Res 44(13):827-33 CrossRef
13. Ely D, Underwood A, Dunphy G, Boehme S, Turner M, Milsted A (2010) Review of the Y chromosome, Sry and hypertension. Steroids 75(11):747-53 CrossRef
14. Engel N, Thorvaldsen JL, Bartolomei MS (2006) CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus. Hum Mol Genet 15(19):2945-954 CrossRef
15. Enoch MA (2006) Genetic and environmental influences on the development of alcoholism: resilience vs. risk. Ann N Y Acad Sci 1094:193-01 CrossRef
16. Fodor M, Delemarre-van de Waal HA (2001) Are POMC neurons targets for sex steroids in the arcuate nucleus of the rat? Neuroreport 12(18):3989-991 CrossRef
17. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A 89(5):1827-831 CrossRef
18. H?rk?nen K, Huhtaniemi I, M?kinen J, Hübler D, Irjala K, Koskenvuo M, Oettel M, Raitakari O, Saad F, P?ll?nen P (2003) The polymorphic androgen receptor gene CAG repeat, pituitary–testicular function and andropausal symptoms in ageing men. Int J Androl 26(3):187-94 CrossRef
19. Heberlein A, Muschler M, Frieling H, Lenz B, Wilhelm J, Gr?schl M, Kornhuber J, Bleich S, Hillemacher T (2011) Decreased galanin serum levels are associated with alcohol-craving during withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 35(2):568-72 CrossRef
20. Heberlein A, Muschler M, Frieling H, Behr M, Eberlein C, Wilhelm J, Gr?schl M, Kornhuber J, Bleich S, Hillemacher T (2013) Epigenetic down regulation of nerve growth factor during alcohol withdrawal. Addict Biol 18:508-10 CrossRef
21. Irvine RA, Ma H, Yu MC, Ross RK, Stallcup MR, Coetzee GA (2000) Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length. Hum Mol Genet 9(2):267-74 CrossRef
22. Kraus J, Buchfelder M, Hollt V (1993) Regulatory elements of the human proopiomelanocortin gene promoter. DNA Cell Biol 12(6):527-36 CrossRef
23. Lamolet B, Pulichino AM, Lamonerie T, Gauthier Y, Brue T, Enjalbert A, Drouin J (2001) A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell 104(6):849-59 CrossRef
24. Laudet V, Auwerx J, Gustafsson J-A, Wahli W (1999) A unified nomenclature system for the nuclear receptor superfamily. Cell 97(2):161-63 CrossRef
25. Lee YS (2009) The role of leptin–melanocortin system and human weight regulation: lessons from experiments of nature. Ann Acad Med Singapore 38(1):34-1
26. Leithoff H (1963) An automatic method of blood alcohol determination. Med Welt 17:959-63
27. Lenz B, Jacob C, Frieling H, Jacobi A, Hillemacher T, Muschler M, Watson K, Kornhuber J, Bleich S (2009) Polymorphism of the long polyglutamine tract in the human androgen receptor influences craving of men in alcohol withdrawal. Psychoneuroendocrinology 34(7):968-71 CrossRef
28. Lenz B, Frieling H, Jacob C, Heberlein A, Kornhuber J, Bleich S, Hillemacher T (2010a) The modulating effect of the androgen receptor on craving in alcohol withdrawal of men is partially mediated by leptin. Pharmacogenomics J 10:226-31 CrossRef
29. Lenz B, Frieling H, Jacob C, Heberlein A, Kornhuber J, Bleich S, Hillemacher T (2010b) The modulating effect of the androgen receptor on craving in alcohol withdrawal of men is partially mediated by leptin. Pharmacogenomics J 10(3):226-31 CrossRef
30. Lenz B, Müller CP, Stoessel C, Sperling W, Biermann T, Hillemacher T, Bleich S, Kornhuber J (2012) Sex hormone activity in alcohol addiction: integrating organizational and activational effects. Prog Neurobiol 96(1):136-63
31. Lewin J, Schmitt AO, Adorjan P, Hildmann T, Piepenbrock C (2004) Quantitative DNA methylation analysis based on four-dye trace data from direct sequencing of PCR amplificates. Bioinformatics 20(17):3005-012 CrossRef
32. Macleod D, Charlton J, Mullins J, Bird AP (1994) Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev 8(19):2282-292 CrossRef
33. Mayer A, Lahr G, Swaab DF, Pilgrim C, Reisert I (1998) The Y-chromosomal genes SRY and ZFY are transcribed in adult human brain. Neurogenetics 1(4):281-88 CrossRef
34. Mooradian AD, Morley JE, Korenman SG (1987) Biological actions of androgens. Endocr Rev 8(1):1-8 CrossRef
35. Muschler MA, Hillemacher T, Kraus C, Kornhuber J, Bleich S, Frieling H (2010) DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. J Neural Transm 117(4):513-19 CrossRef
36. Newell-Price J, King P, Clark AJ (2001) The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol 15(2):338-48 CrossRef
37. Richardson HN, Lee SY, O'Dell LE, Koob GF, Rivier CL (2008) Alcohol self-administration acutely stimulates the hypothalamic–pituitary–adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state. Eur J Neurosci 28(8):1641-653 CrossRef
38. Schneider G, Nienhaus K, Gromoll J, Heuft G, Nieschlag E, Zitzmann M (2011) Depressive symptoms in men aged 50 years and older and their relationship to genetic androgen receptor polymorphism and sex hormone levels in three different samples. Am J Geriatr Psychiatry 19:274-83 CrossRef
39. Seidman SN, Araujo AB, Roose SP, McKinlay JB (2001) Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men. Biol Psychiatry 50(5):371-76 CrossRef
40. Singh K, Prasad S (2008) Age- and sex-related analysis of methylation of 5'-upstream sequences of Fmr-1 gene in mouse brain and modulation by sex steroid hormones. Biogerontology 9(6):455-65 CrossRef
41. Soyka M, Helten C, Schmidt P (2010) OCDS craving scores predict 24-month outcome in alcoholic outpatients. Am J Addict 19(3):264-69 CrossRef
42. Stevens A, Begum G, Cook A, Connor K, Rumball C, Oliver M, Challis J, Bloomfield F, White A (2010) Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition. Endocrinology 151(8):3652-664 CrossRef
43. Stevens A, Begum G, White A (2011) Epigenetic changes in the hypothalamic pro-opiomelanocortin gene: a mechanism linking maternal undernutrition to obesity in the offspring? Eur J Pharmacol 660(1):194-01 CrossRef
44. Su QR, Su LY, Su HR, Chen Q, Ren GY, Yin Y, Shen SQ, Yu AY, Xia GY (2007) Polymorphisms of androgen receptor gene in childhood and adolescent males with first-onset major depressive disorder and association with related symptomatology. Int J Neurosci 117(7):903-17 CrossRef
45. Travison TG, Shackelton R, Araujo AB, Morley JE, Williams RE, Clark RV, McKinlay JB (2010) Frailty, serum androgens, and the CAG repeat polymorphism: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 95(6):2746-754 CrossRef
46. Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL (1997) Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 82(11):3777-782
47. Vermeersch H, T'Sjoen G, Kaufman JM, Vincke J, Van Houtte M (2010) Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males. Eur J Endocrinol 163(2):319-28 CrossRef
48. Wang SS, Kamphuis W, Huitinga I, Zhou JN, Swaab DF (2008) Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol Psychiatry 13(8):786-99, 741 CrossRef
49. Westberg L, Baghaei F, Rosmond R, Hellstrand M, Landen M, Jansson M, Holm G, Bjorntorp P, Eriksson E (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(6):2562-568
50. World Health Organization (2004) ICD-10: international statistical classification of diseases and related health problems. World Health Organization, Geneva
51. Yuan X, Lu ML, Li T, Balk SP (2001) SRY interacts with and negatively regulates androgen receptor transcriptional activity. J Biol Chem 276(49):46647-6654 CrossRef - 作者单位：Marc Andre Nicolas Muschler (1) (2)
Bernd Lenz (2)
Thomas Hillemacher (1) (2)
Cornelia Kraus (3)
Johannes Kornhuber (2)
Helge Frieling (1) (2)
Stefan Bleich (1) (2)
1. Department of Psychiatry, Socialpsychiatry and Psychotherapy, Center for Addiction Research, Hannover Medical School, Carl-Neuberg-Stra?e 1, 30625, Hannover, Germany
2. Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen—Nuremberg, Erlangen, Germany
3. Institute of Human Genetics, University Hospital of Erlangen, Friedrich-Alexander-University Erlangen—Nuremberg, Erlangen, Germany - ISSN：1432-2072
文摘
Rationale Previous findings of the Franconian Alcoholism Research Studies showed that both the CAGn of the androgen receptor (AR) and the promoter methylation of the hypothalamic peptide proopiomelanocortin (POMC) were associated with craving of male alcohol-dependent patients. Objectives Based on the strong interactions between the hypothalamic–pituitary–gonadal (HPG) and the hypothalamic–pituitary–adrenal axis (HPA), this study investigated the relationships between the CAGn repeat of the AR, POMC promoter methylation and craving of male alcohol-dependent patients. Methods This analysis covers 84 male patients with a diagnosis of alcohol dependence (DSM-IV). We sequenced the POMC gene promoter using bisulfite modified DNA to display the methylation status. Furthermore, we sequenced the CAGn repeat within exon 1 of the AR gene. Craving was quantified by the Obsessive Compulsive Drinking Scale. Results We found an inverse correlation between the number of CAGn repeats of the AR and the POMC methylation status in this study. Altogether, the POMC promoter methylation accounted for 33?% of the relationship between CAGn AR polymorphism and craving. Conclusions This work shows that the AR and the POMC gene might functionally interact with each other and subsequently mediate craving in alcohol-dependent patients. The paper discusses different mechanisms which might underlie our findings involving sex hormones' and sex determining region of Y-gene's regulatory function on DNA-methyltransferase activity. In conclusion, the results give insight in the interaction between HPG and HPA axis. This study is a further step on the way to a better understanding of genetic and non-genetic factors underlying craving for alcohol.