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Genetik der androgenetischen Alopezie

Genetics of androgenetic alopecia

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medizinische genetik

Zusammenfassung

Die androgenetische Alopezie (AGA, erblich- bzw. hormonbedingter Haarausfall [MIM 109200; MIM 300710; MIM 612421]) ist die häufigste Form des Haarverlusts beim Menschen, wobei die Prävalenz stark altersabhängig ist. Im Alter von über 70 Jahren sind über 80% der europäischen Männer betroffen, bei Frauen liegt die AGA-Häufigkeit mit 30–40% deutlich niedriger. Die AGA führt, v. a. bei betroffenen Frauen, zu einer erheblichen psychologischen Belastung und entfaltet dabei Krankheitswert. Der Haarverlust geht auf einen veränderten Haarzyklus und eine Miniaturisierung des Haarfollikels zurück. Die Pathogenese ist androgenabhängig, und die genetische Anlage ist wesentliche Voraussetzung für den Phänotyp. In mehreren Studien konnten der Androgenrezeptor-/Ektodysplasin-A2-Rezeptor(EDA2R)-Locus auf dem X-Chromosom als stärkster beitragender Faktor und durch genomweite Assoziationsuntersuchungen ein weiterer Locus auf Chromosom 20p11 identifiziert werden. Das zum Assoziationssignal nächstgelegene in der Kopfhaut exprimierte Gen ist „paired box 1“ (PAX1). Zwischen PAX1 und dem Androgensignalweg gibt es keine offensichtliche Verbindung, jedoch sind die dem Assoziationssignal auf Chromosom 20p11 zugrunde liegenden pathophysiologischen Prozesse noch nicht geklärt. Bis heute ermöglichen die zur Verfügung stehenden medikamentösen Therapien der AGA bestenfalls ein Aufhalten des Haarverlusts. Mit der Identifizierung der AGA-assoziierten Gene und der Aufklärung ihrer Funktionen wird man die biologischen Ursachen der AGA schrittweise erschließen. Damit ist die Hoffnung auf die Entwicklung neuer Therapien verbunden.

Abstract

Androgenetic alopecia (AGA, male pattern baldness [MIM 109200; MIM 300710; MIM 612421]) is the commonest form of hair loss in humans, and its prevalence is highly age-dependent. Eighty per cent of European men above the age of 70 are affected by AGA, but only 30–40% of women. In many affected individuals, particularly women, AGA causes clinically significant psychological distress. Hair loss is attributable to an altered hair cycle and miniaturization of the hair follicles. The pathogenesis is androgen dependent, and genetic predisposition is an essential prerequisite of the phenotype. Several studies have identified the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome as the strongest contributing factor. Genome wide association studies have identified a further locus on chromosome 20p11. The nearest scalp expressed gene to the association signal is paired box 1 (PAX1). Although there is no obvious connection between PAX1 and the androgen signalling pathway, the pathophysiological processes underlying the association signal for chromosome 20p11 have not yet been explained. At best, currently available therapies for AGA permit the arrest of hair loss. The identification of AGA associated genes and the elucidation of their function will gradually reveal the biological causes of AGA and offer hope for the development of new therapies.

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Literatur

  1. Ahouansou S, Le Toumelin P, Crickx B, Descamps V (2007) Association of androgenetic alopecia and hypertension. Eur J Dermatol 17:220–222

    PubMed  Google Scholar 

  2. Andersson S, Berman DM, Jenkins EP, Russell DW (1991) Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature 354:159–161

    Article  CAS  PubMed  Google Scholar 

  3. Bergfeld WF (1995) Androgenetic alopecia: an autosomal dominant disorder. Am J Med 98:95S–98S

    Article  CAS  PubMed  Google Scholar 

  4. Bienova M, Kucerova R, Fiuraskova M et al (2005) Androgenetic alopecia and current methods of treatment. Acta Dermatovenerol Alp Panonica Adriat 14:5–8

    PubMed  Google Scholar 

  5. Birch MP, Messenger AG (2001) Genetic factors predispose to balding and non-balding in men. Eur J Dermatol 11:309–314

    CAS  PubMed  Google Scholar 

  6. Birch MP, Messenger JF, Messenger AG (2001) Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol 144:297–304

    Article  CAS  PubMed  Google Scholar 

  7. Braun-Falco O, Bergner T (1989) Androgenetic alopecia in the male. Recent developments. Hautarzt 40:669–678

    CAS  PubMed  Google Scholar 

  8. Brockschmidt FF, Hillmer AM, Eigelshoven S et al (eingereicht) Fine mapping of the human AR/EDA2R locus in androgenetic alopecia.

  9. Brockschmidt FF, Nöthen MM, Hillmer AM (2007) The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function. J Mol Endocrinol 39:1–8

    Article  CAS  PubMed  Google Scholar 

  10. Brown CJ, Goss SJ, Lubahn DB et al (1989) Androgen receptor locus on the human X chromosome: regional localization to Xq11–12 and description of a DNA polymorphism. Am J Hum Genet 44:264–269

    CAS  PubMed  Google Scholar 

  11. Carey AH, Chan KL, Short F et al (1993) Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf) 38:653–658

    Google Scholar 

  12. Cash TF (1992) The psychological effects of androgenetic alopecia in men. J Am Acad Dermatol 26:926–931

    Article  CAS  PubMed  Google Scholar 

  13. Chen Y, Zajac JD, MacLean HE (2005) Androgen regulation of satellite cell function. J Endocrinol 186:21–31

    Article  CAS  PubMed  Google Scholar 

  14. Cipriani R, Ruzza G, Foresta C et al (1983) Sex hormone-binding globulin and saliva testosterone levels in men with androgenetic alopecia. Br J Dermatol 109:249–252

    Article  CAS  PubMed  Google Scholar 

  15. Courtois M, Loussouarn G, Hourseau C, Grollier JF (1994) Hair cycle and alopecia. Skin Pharmacol Physiol 7:84–89

    Article  CAS  Google Scholar 

  16. Ding D, Xu L, Menon M et al (2005) Effect of GGC (glycine) repeat length polymorphism in the human androgen receptor on androgen action. Prostate 62:133–139

    Article  CAS  PubMed  Google Scholar 

  17. Ellis JA, Scurrah KJ, Cobb JE et al (2007) Baldness and the androgen receptor: the AR polyglycine repeat polymorphism does not confer susceptibility to androgenetic alopecia. Hum Genet 121:451–457

    Article  PubMed  Google Scholar 

  18. Ellis JA, Sinclair R, Harrap SB (2002) Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med 4:1–11

    Article  Google Scholar 

  19. Ellis JA, Stebbing M, Harrap SB (2001) Polymorphism of the androgen receptor gene is associated with male pattern baldness. J Invest Dermatol 116:452–455

    Article  CAS  PubMed  Google Scholar 

  20. Ford ES, Freedman DS, Byers T (1996) Baldness and ischemic heart disease in a national sample of men. Am J Epidemiol 143:651–657

    CAS  PubMed  Google Scholar 

  21. Giles GG, Severi G, Sinclair R et al (2002) Androgenetic alopecia and prostate cancer: findings from an Australian case-control study. Cancer Epidemiol Biomarkers Prev 11:549–553

    PubMed  Google Scholar 

  22. Griffin JE, Wilson JD (1989) The androgen resistance syndromes: 5alpha-reductase deficiency, testicular feminisation and related disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1919–1944

  23. Group FMPHLS (2002) Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia. Eur J Dermatol 12:38–49

    Google Scholar 

  24. Hamilton JB (1942) Male hormone stimulation is a prerequisite and an incitant in common baldness. Am J Anat 71:451–480

    Article  Google Scholar 

  25. Hamilton JB (1951) Patterned loss of hair in man; types and incidence. Ann N Y Acad Sci 53:708–728

    Article  CAS  PubMed  Google Scholar 

  26. Hanneken S, Ritzmann S, Nöthen MM, Kruse R (2003) Androgenetische Alopezie: Aktuelle Aspekte eines vertrauten Phänotyps. Hautarzt 54:703–712

    Article  CAS  PubMed  Google Scholar 

  27. Hawk E, Breslow RA, Graubard BI (2000) Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the first National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev 9:523–527

    CAS  PubMed  Google Scholar 

  28. Hayes VM, Severi G, Eggleton SA et al (2005) The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. Cancer Epidemiol Biomarkers Prev 14:993–996

    Article  CAS  PubMed  Google Scholar 

  29. Herrera CR, D’Agostino RB, Gerstman BB et al (1995) Baldness and coronary heart disease rates in men from the Framingham Study. Am J Epidemiol 142:828–833

    CAS  PubMed  Google Scholar 

  30. Hibberts NA, Howell AE, Randall VA (1998) Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. J Endocrinol 156:59–65

    Article  CAS  PubMed  Google Scholar 

  31. Hillmer AM, Brockschmidt FF, Hanneken S et al (2008) Susceptibility variants for male-pattern baldness on chromosome 20p11. Nat Genet 40:1279–1281

    Article  CAS  PubMed  Google Scholar 

  32. Hillmer AM, Flaquer A, Hanneken S et al (2008) Genome-wide scan and fine-mapping linkage study of androgenetic alopecia reveals a locus on chromosome 3q26. Am J Hum Genet 82:737–743

    Article  CAS  PubMed  Google Scholar 

  33. Hillmer AM, Freudenberg J, Myles S et al (2009) Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness. Hum Genet 126:255–264

    Article  CAS  PubMed  Google Scholar 

  34. Hillmer AM, Hanneken S, Ritzmann S et al (2005) Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am J Hum Genet 77:140–148

    Article  CAS  PubMed  Google Scholar 

  35. Hirsso P, Laakso M, Matilainen V et al (2006) Association of insulin resistance linked diseases and hair loss in elderly men. Finnish population-based study. Cent Eur J Public Health 14:78–81

    PubMed  Google Scholar 

  36. Hirsso P, Rajala U, Hiltunen L et al (2007) Obesity and low-grade inflammation among young Finnish men with early-onset alopecia. Dermatology 214:125–129

    PubMed  Google Scholar 

  37. Hoffman RM (2005) Gene and stem cell therapy of the hair follicle. Methods Mol Biol 289:437–448

    PubMed  Google Scholar 

  38. Hoffmann R, Niiyama S, Huth A et al (2002) 17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo. Exp Dermatol 11:376–380

    Article  CAS  PubMed  Google Scholar 

  39. Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974) Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 186:1213–1215

    Article  CAS  PubMed  Google Scholar 

  40. Kaufman KD (2002) Androgens and alopecia. Mol Cell Endocrinol 198:89–95

    Article  CAS  PubMed  Google Scholar 

  41. Kaufman KD, Olsen EA, Whiting D et al (1998) Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 39:578–589

    Article  CAS  PubMed  Google Scholar 

  42. Küster W, Happle R (1984) The inheritance of common baldness: two B or not two B? J Am Acad Dermatol 11:921–926

    Article  PubMed  Google Scholar 

  43. Lee AT, Zane LT (2007) Dermatologic manifestations of polycystic ovary syndrome. Am J Clin Dermatol 8:201–219

    Article  PubMed  Google Scholar 

  44. Lee HJ, Chang C (2003) Recent advances in androgen receptor action. Cell Mol Life Sci 60:1613–1622

    Article  CAS  PubMed  Google Scholar 

  45. Levy-Nissenbaum E, Bar-Natan M, Frydman M, Pras E (2005) Confirmation of the association between male pattern baldness and the androgen receptor gene. Eur J Dermatol 15:339–340

    CAS  PubMed  Google Scholar 

  46. Lotufo PA, Chae CU, Ajani UA et al (2000) Male pattern baldness and coronary heart disease: the Physicians‘ Health Study. Arch Intern Med 160:165–171

    Article  CAS  PubMed  Google Scholar 

  47. Ludwig E (1977) Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol 97:247–254

    Article  CAS  PubMed  Google Scholar 

  48. Lundin KB, Giwercman A, Dizeyi N, Giwercman YL (2007) Functional in vitro characterisation of the androgen receptor GGN polymorphism. Mol Cell Endocrinol 264:184–187

    Article  CAS  PubMed  Google Scholar 

  49. Mangelsdorf DJ, Thummel C, Beato M et al (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839

    Article  CAS  PubMed  Google Scholar 

  50. Matias JR, Malloy V, Orentreich N (1989) Animal models of androgen-dependent disorders of the pilosebaceous apparatus. 1. The androchronogenetic alopecia (AGA) mouse as a model for male-pattern baldness. Arch Dermatol Res 281:247–253

    Article  CAS  PubMed  Google Scholar 

  51. Matilainen V, Koskela P, Keinanen-Kiukaanniemi S (2000) Early androgenetic alopecia as a marker of insulin resistance. Lancet 356:1165–1166

    Article  CAS  PubMed  Google Scholar 

  52. Matilainen VA, Makinen PK, Keinanen-Kiukaanniemi SM (2001) Early onset of androgenetic alopecia associated with early severe coronary heart disease: a population-based, case-control study. J Cardiovasc Risk 8:147–151

    Article  CAS  PubMed  Google Scholar 

  53. Mosley JG, Gibbs AC (1996) Premature grey hair and hair loss among smokers: a new opportunity for health education? BMJ 313:1616

    CAS  PubMed  Google Scholar 

  54. Norwood OT (2001) Incidence of female androgenetic alopecia (female pattern alopecia). Dermatol Surg 27:53–54

    Article  CAS  PubMed  Google Scholar 

  55. Norwood OT (1975) Male pattern baldness: classification and incidence. South Med J 68:1359–1365

    CAS  PubMed  Google Scholar 

  56. Nyholt DR, Gillespie NA, Heath AC, Martin NG (2003) Genetic basis of male pattern baldness. J Invest Dermatol 121:1561–1564

    Article  PubMed  Google Scholar 

  57. Obana NJ, Uno H (1996) Dermal papilla cells in macaque alopecia trigger a testosterone-dependent inhibition of follicular cell proliferation. In: Van Neste D, Randall VA (eds) Hair research in the next millennium. Elsevier, Amsterdam, pp 307–310

  58. Oh BR, Kim SJ, Moon JD et al (1998) Association of benign prostatic hyperplasia with male pattern baldness. Urology 51:744–748

    Article  CAS  PubMed  Google Scholar 

  59. Olsen EA, Messenger AG, Shapiro J et al (2005) Evaluation and treatment of male and female pattern hair loss. J Am Acad Dermatol 52:301–311

    Article  PubMed  Google Scholar 

  60. Osborn D (1916) Inheritance of baldness: various patterns due to heredity and sometimes present at birth— a sex-limited character— dominant in man— women not bald unless they inherit tendency from both parents. J Hered 347–355

  61. Pawlowski JE, Ertel JR, Allen MP et al (2002) Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells. J Biol Chem 277:20.702–20.710

    Article  Google Scholar 

  62. Prodi DA, Pirastu N, Maninchedda G et al (2008) EDA2R is associated with androgenetic alopecia. J Invest Dermatol 128:2268–2270

    Article  CAS  PubMed  Google Scholar 

  63. Randall VA (2007) Hormonal regulation of hair follicles exhibits a biological paradox. Semin Cell Dev Biol 18:274–285

    Article  CAS  PubMed  Google Scholar 

  64. Randall VA (1994) Role of 5 alpha-reductase in health and disease. Baillieres Clin Endocrinol Metab 8:405–431

    Article  CAS  PubMed  Google Scholar 

  65. Rexbye H, Petersen I, Iachina M et al (2005) Hair loss among elderly men: etiology and impact on perceived age. J Gerontol A Biol Sci Med Sci 60:1077–1082

    PubMed  Google Scholar 

  66. Richards JB, Yuan X, Geller F et al (2008) Male-pattern baldness susceptibility locus at 20p11. Nat Genet 40:1282–1284

    Article  CAS  PubMed  Google Scholar 

  67. Rutberg SE, Kolpak ML, Gourley JA et al (2006) Differences in expression of specific biomarkers distinguish human beard from scalp dermal papilla cells. J Invest Dermatol 126:2583–2595

    Article  CAS  PubMed  Google Scholar 

  68. Sawaya ME (1999) Androgenetic alopecia: overview. J Cutan Med Surg [Suppl 3] 3:S14–S20

  69. Sawaya ME, Price VH (1997) Different levels of 5alpha-reductase type I and II, aromatase and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol 109:296–300

    Article  CAS  PubMed  Google Scholar 

  70. Sawaya ME, Shalita AR (1998) Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopecia, hirsutism and acne. J Cutan Med Surg 3:9–15

    CAS  PubMed  Google Scholar 

  71. Schnohr P, Lange P, Nyboe J et al (1995) Gray hair, baldness, and wrinkles in relation to myocardial infarction: the Copenhagen City Heart Study. Am Heart J 130:1003–1010

    Article  CAS  PubMed  Google Scholar 

  72. Sinclair R (1998) Male pattern androgenetic alopecia. BMJ 317:865–869

    CAS  PubMed  Google Scholar 

  73. Sprecher E, Shalata A, Dabhah K et al (2000) Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene. J Am Acad Dermatol 42:978–982

    Article  CAS  PubMed  Google Scholar 

  74. Stenn KS, Paus R (2001) Controls of hair follicle cycling. Physiol Rev 81:449–494

    CAS  PubMed  Google Scholar 

  75. Stough D, Stenn K, Haber R et al (2005) Psychological effect, pathophysiology, and management of androgenetic alopecia in men. Mayo Clin Proc 80:1316–1322

    Article  PubMed  Google Scholar 

  76. Sundberg JP, Beamer WG, Uno H et al (1999) Androgenetic alopecia: in vivo models. Exp Mol Pathol 67:118–130

    Article  CAS  PubMed  Google Scholar 

  77. Tosti A, Camacho-Martinez F, Dawber R (1999) Management of androgenetic alopecia. J Eur Acad Dermatol Venereol 12:205–214

    Article  CAS  PubMed  Google Scholar 

  78. Tosti A, Piraccini BM (1999) Androgenetic alopecia. Int J Dermatol [Suppl 1] 38:1–7

    Google Scholar 

  79. Tran D, Sinclair RD (1999) Understanding and managing common baldness. Aust Fam Physician 28:248–250, 252–243

    CAS  PubMed  Google Scholar 

  80. Tyagi RK, Lavrovsky Y, Ahn SC et al (2000) Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells. Mol Endocrinol 14:1162–1174

    Article  CAS  PubMed  Google Scholar 

  81. Unger WP, Unger RH (2003) Hair transplanting: an important but often forgotten treatment for female pattern hair loss. J Am Acad Dermatol 49:853–860

    Article  PubMed  Google Scholar 

  82. Wang L, Hsu CL, Chang C (2005) Androgen receptor corepressors: an overview. Prostate 63:117–130

    Article  CAS  PubMed  Google Scholar 

  83. Wang Q, Udayakumar TS, Vasaitis TS et al (2004) Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells. J Biol Chem 279:17.319–17.328

    Google Scholar 

  84. Whiting DA (1993) Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. J Am Acad Dermatol 28:755–763

    Article  CAS  PubMed  Google Scholar 

  85. Whiting DA (1998) Male pattern hair loss: current understanding. Int J Dermatol 37:561–566

    Article  CAS  PubMed  Google Scholar 

  86. Whiting DA (2001) Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. J Am Acad Dermatol 45:S81–S86

    Article  CAS  PubMed  Google Scholar 

  87. Winiarska A, Mandt N, Kamp H et al (2006) Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells. Skin Pharmacol Physiol 19:311–321

    Article  CAS  PubMed  Google Scholar 

  88. Yip L, Zaloumis S, Irwin D et al (2009) Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. Br J Dermatol 161:289–294

    Article  CAS  PubMed  Google Scholar 

  89. Zhou ZX, Lane MV, Kemppainen JA et al (1995) Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability. Mol Endocrinol 9:208–218

    Article  CAS  PubMed  Google Scholar 

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  1. Institut für Humangenetik, Universität Bonn, Wilhelmstraße 31, 53111, Bonn, Deutschland

    F.F. Brockschmidt &  M.M. Nöthen

  2. Abteilung für Genomik, Forschungszentrum Life & Brain, Universität Bonn, Bonn, Deutschland

    F.F. Brockschmidt &  M.M. Nöthen

  3. Genome Technology & Biology Group, Genome Institute of Singapore, Singapore, Singapore

    A.M. Hillmer

  4. Hautklinik, Universität Düsseldorf, Düsseldorf, Deutschland

    R. Kruse

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  1. F.F. Brockschmidt
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Brockschmidt, F., Hillmer, A., Kruse, R. et al. Genetik der androgenetischen Alopezie. medgen 21, 511–518 (2009). https://doi.org/10.1007/s11825-009-0197-0

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