Advertisement

Acne Epidemiology and Genetics

  • Gerd Plewig
  • Bodo Melnik
  • WenChieh Chen
Chapter

Abstract

There is substantial evidence that hereditary factors play an important role in acne pathogenesis. They enhance the risk for disease or aggravate its course and outcome and modify the time of onset, persistence after puberty, response to treatment, tissue remodeling and healing, the extent of scaring, and the disposition for keloid. Acne genetics have been overestimated during the last decades because a single genetic polymorphism or a rare mutation cannot explain the high and fast raising prevalence rates in adolescents living in developed countries. The high acne prevalence in developed countries underlines the predominance of environmental factors including Western-style nutrition.

Bibliography

  1. Addor FA, Schalka S. Acne in adult women: epidemiological, diagnostic and therapeutic aspects. An Bras Dermatol. 2010;85:789.PubMedGoogle Scholar
  2. Agodi A, Barchitta M, Valenti G, et al. Role of the TNFA -308G > A polymorphism in the genetic susceptibility to acne vulgaris in a Sicilian population. Ann Ig. 2012;24:351–7.PubMedGoogle Scholar
  3. Ahmed Z, Schuller AC, Suhling K, et al. Extracellular point mutations in FGFR2 elicit unexpected changes in intracellular signalling. Biochem J. 2008;413:37–49.PubMedGoogle Scholar
  4. Aisha NM, Haroon J, Hussain S, et al. Association between tumour necrosis-α gene polymorphisms and acne vulgaris in a Pakistani population. Clin Exp Dermatol. 2016;41:297–301.PubMedGoogle Scholar
  5. Al-Shobaili HA, Salem TA, Alzolibani AA, et al. Tumor necrosis factor-α −308 G/A and interleukin 10–1082 A/G gene polymorphisms in patients with acne vulgaris. J Dermatol Sci. 2012;68:52–5.PubMedGoogle Scholar
  6. Alzoubi KH, Khabour OF, Hassan RE, et al. The effect of genetic polymorphisms of RARA gene on the adverse effects profile of isotretinoin-treated acne patients. Int J Clin Pharmacol Ther. 2013;51:631–40.PubMedGoogle Scholar
  7. Ando I, Kukita A, Soma G, Hino H. A large number of tandem repeats in the polymorphic epithelial mucin gene is associated with severe acne. J Dermatol. 1998;25:150–2.PubMedGoogle Scholar
  8. Assmann G, Wagner AD, Monika M, et al. Single-nucleotide polymorphisms p53 G72C and Mdm2 T309G in patients with psoriasis, psoriatic arthritis, and SAPHO syndrome. Rheumatol Int. 2010;30:1273–6.PubMedGoogle Scholar
  9. Bagatin E, Timpano DL, Guadanhim LR, et al. Acne vulgaris: prevalence and clinical forms in adolescents from São Paulo, Brazil. An Bras Dermatol. 2014;89:428–35.PubMedPubMedCentralGoogle Scholar
  10. Ballanger F, Baudry P, N’Guyen JM, et al. Heredity: a prognostic factor for acne. Dermatology. 2006;212:145–9.PubMedGoogle Scholar
  11. Bataille V, Snieder H, MacGregor AJ, et al. The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women. J Invest Dermatol. 2002;119:1317–22.PubMedGoogle Scholar
  12. Baz K, Emin Erdal M, Yazici AC, et al. Association between tumor necrosis factor-alpha gene promoter polymorphism at position −308 and acne in Turkish patients. Arch Dermatol Res. 2008;300:371–6.PubMedGoogle Scholar
  13. Bechelli LM, Haddad N, Pimenta WP, et al. Epidemiological survey of skin diseases in schoolchildren living in the Purus Valley (Acre State, Amazonia, Brazil). Dermatologica. 1981;163:78–93.PubMedGoogle Scholar
  14. Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474–85.PubMedGoogle Scholar
  15. Capitanio B, Sinagra JL, Bordignon V, et al. Underestimated clinical features of postadolescent acne. J Am Acad Dermatol. 2010;63:782–8.PubMedGoogle Scholar
  16. Chamaie-Nejad F, Saeidi S, Najafi F, et al. Association of the CYP17 MSP AI (T-34C) and CYP19 codon 39 (Trp/Arg) polymorphisms with susceptibility to acne vulgaris. Clin Exp Dermatol. 2018;43:183–6.PubMedGoogle Scholar
  17. Chang SW, Su CH, Chen HH, et al. DDB2 is a novel AR interacting protein and mediates AR ubiquitination/degradation. Int J Biochem Cell Biol. 2012;44:1952–61.PubMedGoogle Scholar
  18. Chlebus E, Chlebus M. Factors affecting the course and severity of adult acne. Observational cohort study. J Dermatolog Treat. 2017;28:737–44.PubMedGoogle Scholar
  19. Choi CW, Lee DH, Kim HS, et al. The clinical features of late onset acne compared with early onset acne in women. J Eur Acad Dermatol Venereol. 2011;25:454–61.PubMedGoogle Scholar
  20. Collier CN, Harper JC, Cafardi JA, et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58:56–9.PubMedGoogle Scholar
  21. Cordain L, Lindeberg S, Hurtado M, et al. Acne vulgaris: a disease of Western civilization. Arch Dermatol. 2002;138:1584–90.PubMedGoogle Scholar
  22. Dréno B, Layton A, Zouboulis CC, et al. Adult female acne: a new paradigm. J Eur Acad Dermatol Venereol. 2013;27:1063–70.PubMedGoogle Scholar
  23. Dréno B, Thiboutot D, Layton AM, et al. Large-scale international study enhances understanding of an emerging acne population: adult females. J Eur Acad Dermatol Venereol. 2015;29:1096–106.PubMedGoogle Scholar
  24. Ehm MG, Aponte JL, Chiano MN, et al. Phenome-wide association study using research participants’ self-reported data provides insight into the Th17 and IL-17 pathway. PLoS One. 2017;12:e0186405.PubMedPubMedCentralGoogle Scholar
  25. Evans DM, Kirk KM, Nyholt DR, et al. Teenage acne is influenced by genetic factors. Br J Dermatol. 2005;152:565–95.Google Scholar
  26. Friedman GD. Twin studies of disease heritability based on medical records: application to acne vulgaris. Acta Genet Med Gemellol. 1984;33:487–95.PubMedGoogle Scholar
  27. Geusau A, Mothes-Luksch N, Nahavandi H, et al. Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment. JAMA Dermatol. 2013;149:209–15.PubMedGoogle Scholar
  28. Ghodsi SZ, Orawa H, Zouboulis CC. Prevalence, severity, and severity risk factors of acne in high school pupils: a community-based study. J Invest Dermatol. 2009;129:2136–41.PubMedGoogle Scholar
  29. Glickman FS, Silvers SH. Dietary factors in acne vulgaris. Arch Dermatol. 1972;106:129.PubMedGoogle Scholar
  30. Goldberg JL, Dabade TS, Davis SA, et al. Changing age of acne vulgaris visits: another sign of earlier puberty? Pediatr Dermatol. 2011;28:645–8.PubMedGoogle Scholar
  31. Gomis RR, Alarcón C, He W, et al. A FoxO-Smad synexpression group in human keratinocytes. Proc Natl Acad Sci U S A. 2006;103:12747–52.PubMedPubMedCentralGoogle Scholar
  32. Goulden V, McGeown CH, Cunliffe WJ. The familial risk of adult acne: a comparison between first-degree relatives of affected and unaffected individuals. Br J Dermatol. 1999a;141:297–300.PubMedGoogle Scholar
  33. Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999b;41:577–80.PubMedGoogle Scholar
  34. Grech I, Giatrakos S, Damoraki G, et al. Impact of TNF haplotypes in the physical course of acne vulgaris. Dermatology. 2012;228:152–7.Google Scholar
  35. Han XD, Oon HH, Goh CL. Epidemiology of post-adolescence acne and adolescence acne in Singapore: a 10-year retrospective and comparative study. J Eur Acad Dermatol Venereol. 2016;30:1790–3.PubMedGoogle Scholar
  36. He L, Yang Z, Yu H, et al. The relationship between CYP17 -34T/C polymorphism and acne in Chinese subjects revealed by sequencing. Dermatology. 2006;212:338–42.PubMedGoogle Scholar
  37. He L, Wu WJ, Yang JK, et al. Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne. Nat Commun. 2014;5:2870.PubMedGoogle Scholar
  38. Hecht H. Heredity trends in acne vulgaris. Dermatologica. 1960;121:297–307.PubMedGoogle Scholar
  39. Herane MI, Ando I. Acne in infancy and acne genetics. Dermatology. 2003;206:24–8.PubMedGoogle Scholar
  40. Holzmann R, Shakery K. Postadolescent acne in females. Skin Pharmacol Physiol. 2014;27(Suppl 1):3–8.PubMedGoogle Scholar
  41. Hu X, Ding W, Jin X, et al. Longer TA repeat but not V89L polymorphisms in the SRD5A2 gene may confer acne risk in the Chinese population. Adv Dermatol Allergol. 2018;35:33–8.Google Scholar
  42. Hussain S, Iqbal T, Sadiq I, et al. Polymorphism in the IL-8 gene promoter and the risk of acne vulgaris in a Pakistani population. Iran J Allergy Asthma Immunol. 2015a;14:443–9.PubMedGoogle Scholar
  43. Hussain S, Faraz A, Iqbal T. The RETN gene rs1862513 polymorphism as a novel predisposing marker for familial acne vulgaris in a Pakistani population. Iran J Basic Med Sci. 2015b;18:526–8.PubMedPubMedCentralGoogle Scholar
  44. Ibrahim AA, Salem RM, El-Shimi OS, et al. IL1A (−889) gene polymorphism is associated with the effect of diet as a risk factor in acne vulgaris. J Cosmet Dermatol. 2019;18:333–6.PubMedGoogle Scholar
  45. Imperato-McGinley J, Gautier T, Cai LQ, et al. The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab. 1993;76:524–8.PubMedGoogle Scholar
  46. Khunger N, Kumar C. A clinico-epidemiological study of adult acne: is it different from adolescent acne? Indian J Dermatol Venereol Leprol. 2012;78:335–41.PubMedGoogle Scholar
  47. Kirk KM, Evans DM, Farthing B, Martin NG. Genetic and environmental influences on acne in adolescent twins. Twin Res. 2001;4:190.Google Scholar
  48. Koreck A, Kis K, Szegedi K, et al. TLR2 and TLR4 polymorphisms are not associated with acne vulgaris. Dermatology. 2006;213:267–9.PubMedGoogle Scholar
  49. Kovács D, Lovászi M, Póliska S, et al. Sebocytes differentially express and secrete adipokines. Exp Dermatol. 2016;25:194–9.PubMedGoogle Scholar
  50. Li L, Wu Y, Li L, et al. Tumour necrosis factor (TNF)-α is considered to play a central role in the pathogenesis of acne. Clin Exp Dermatol. 2015;40:682–7.PubMedGoogle Scholar
  51. Lichtenberger R, Simpson MA, Smith C, et al. Genetic architecture of acne vulgaris. J Eur Acad Dermatol Venereol. 2017;31:1978–90.PubMedGoogle Scholar
  52. Lindwall E, Singla S, Davis WE, Quinet RJ. Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. Semin Arthritis Rheum. 2015;45:91–3.PubMedGoogle Scholar
  53. Lynn DD, Umari T, Dunnick CA, Dellavalle RP. The epidemiology of acne vulgaris in late adolescence. Adolesc Health Med Ther. 2016;7:13–25.PubMedPubMedCentralGoogle Scholar
  54. Melnik BC. Role of FGFR2-signaling in the pathogenesis of acne. Dermatoendocrinology. 2009;1:141–56.Google Scholar
  55. Melnik BC. Acneigenic stimuli converge in phosphoinositol-3 kinase/Akt/FoxO1 signal transduction. J Clin Exp Dermatol Res. 2010;1:10.Google Scholar
  56. Melnik B, Vakilzadeh F, Aslanidis C, Schmitz G. Unilateral segmental acneiform naevus—a model disorder towards understanding fibroblast growth factor receptor 2 function in acne? Br J Dermatol. 2008;158:1397–9.PubMedGoogle Scholar
  57. Meng X, Pei G, Bai Y, et al. Prevalence of acne vulgaris in Chinese adolescents and adults: a community-based study of 17,345 subjects in six cities. Acta Derm Venereol. 2012;92:40–4.PubMedGoogle Scholar
  58. Mina-Vargas A, Colodro-Conde L, Grasby K, et al. Heritability and GWAS analyses of acne in Australian adolescent twins. Twin Res Hum Genet. 2017;20:541–9.PubMedGoogle Scholar
  59. Munro CS, Wilkie AOM. Epidermal mosaicism producing localized acne: somatic mutation in FGFR2. Lancet. 1998;352:704–5.PubMedGoogle Scholar
  60. Navarini AA, Simpson MA, Weale M, et al. Genome-wide association study identifies three novel susceptibility loci for severe acne vulgaris. Nat Commun. 2014;5:4020.PubMedGoogle Scholar
  61. Osterle LS, Rumsby HP, et al. Carrier status for steroid 21-hydroxylase deficiency is only one factor in the variable phenotype of acne. Clin Endocrinol. 1998;48:209–15.Google Scholar
  62. Pang Y, He CD, Liu Y, et al. Combination of short CAG and GGN repeats in the androgen receptor gene is associated with acne risk in north East China. J Eur Acad Dermatol Venereol. 2008;22:1445–151.PubMedGoogle Scholar
  63. Papakonstantinou E, Aletras AJ, Glass E, et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol. 2005;125:673–84.PubMedGoogle Scholar
  64. Paraskevaidis A, Drakoulis N, Roots I, et al. Polymorphisms in the human cytochrome P-450 1A1 gene (CYP1A1) as a factor for developing acne. Dermatology. 1998;196:171–5.PubMedGoogle Scholar
  65. Perkins AC, Cheng CE, Hillebrand GG, et al. Comparison of the epidemiology of acne vulgaris among Caucasian, Asian, Continental Indian and African American women. J Eur Acad Dermatol Venereol. 2011;25:1054–60.PubMedGoogle Scholar
  66. Perkins AC, Maglione J, Hillebrand GG, et al. Acne vulgaris in women: prevalence across the life span. J Womens Health (Larchmt). 2012;21:223–30.Google Scholar
  67. Rahaman SM, De D, Handa S, et al. Association of insulin-like growth factor (IGF)-1 gene polymorphisms with plasma levels of IGF-1 and acne severity. J Am Acad Dermatol. 2016;75:768–73.PubMedGoogle Scholar
  68. Raina D, Kharbanda S, Kufe D. The MUC1 oncoprotein activates the anti-apoptotic phosphoinositide 3-kinase/Akt and Bcl-xL pathways in rat 3Y1 fibroblasts. J Biol Chem. 2004;279:20607–12.PubMedGoogle Scholar
  69. Sawaya ME, Shalita AR. Androgen receptor polymorphism (CAG repeat length) in androgenetic alopecia, hirsutism, and acne. J Cutan Med Surg. 1998;3:9–15.PubMedGoogle Scholar
  70. Schaefer O. When the Eskimo comes to town. Nutr Today. 1971;6:8–16.Google Scholar
  71. Seattle WI. GBD compare. Seattle: University of Washington; 2013.Google Scholar
  72. Shen Y, Wang T, Zhou C, et al. Necropsies on Okinawans: anatomic and pathologic observations. Arch Pathol. 1946;42:359–80.Google Scholar
  73. Shoham NG, Centola M, Mansfield E, et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci U S A. 2003;100:13501–6.PubMedPubMedCentralGoogle Scholar
  74. Silswal N, Singh AK, Aruna B, et al. Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem Biophys Res Commun. 2005;334:1092–101.PubMedGoogle Scholar
  75. Singh PK, Hollingsworth MA. Cell surface-associated mucins in signal transduction. Trends Cell Biol. 2006;16:467–76.PubMedGoogle Scholar
  76. Skroza N, Tolino E, Mambrin A. Adult acne versus adolescent acne: a retrospective study of 1,167 patients. J Clin Aesthet Dermatol. 2018;11:21–5.PubMedPubMedCentralGoogle Scholar
  77. Smith TM, Gilliland K, Clawson GA, Thiboutot D. IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3 kinase/Akt pathway. J Invest Dermatol. 2008;128:1286–93.Google Scholar
  78. Sobjanek M, Zabłotna M, Nedoszytko B, et al. Lack of association between the promoter polymorphisms at positions −238 and −308 of the tumour necrosis factor alpha gene and acne vulgaris in Polish patients. J Eur Acad Dermatol Venereol. 2009;23:331–2.PubMedGoogle Scholar
  79. Sobjanek M, Zablotna M, Glen J, et al. Polymorphism in interleukin 1A but not in interleukin 8 gene predisposes to acne vulgaris in Polish population. J Eur Acad Dermatol Venereol. 2013;27:259–60.PubMedGoogle Scholar
  80. Sobjanek M, Zabłotna M, Dobosz-Kawałko M, et al. Polymorphisms in the cytochrome P-450 (CYP) 1A1 and 17 genes are not associated with acne vulgaris in the Polish population. Postepy Dermatol Alergol. 2015;32:323–6.PubMedPubMedCentralGoogle Scholar
  81. Szabó K, Tax G, Kis K, et al. Interleukin-1A +4845 (G>T) polymorphism is a factor predisposing to acne vulgaris. Tissue Antigens. 2010;76:411–5.PubMedGoogle Scholar
  82. Szabó K, Tax G, Teodorescu-Brinzeu D, et al. TNFα gene polymorphisms in the pathogenesis of acne vulgaris. Arch Dermatol Res. 2011;303:19–27.PubMedGoogle Scholar
  83. Tasli L, Turgut S, Kacar N, et al. Insulin-like growth factor-I gene polymorphism in acne vulgaris. J Eur Acad Dermatol Venereol. 2013;27:254–7.PubMedGoogle Scholar
  84. Tian LM, Xie HF, Yang T, et al. Association study of tumor necrosis factor receptor type 2 M196R and toll-like receptor 2 Arg753Gln polymorphisms with acne vulgaris in a Chinese Han ethnic group. Dermatology. 2010;221:276–84.PubMedGoogle Scholar
  85. Trivedi NR, Gilliland KL, Zhao W, et al. Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol. 2006;126:1071–9.PubMedGoogle Scholar
  86. Walton S, Wyatt EH, Cunliffe WJ. Genetic control of sebum excretion and acne—a twin study. Br J Dermatol. 1988;118:393–6.PubMedGoogle Scholar
  87. Wang D, Höing S, Patterson HC, et al. Inflammation in mice ectopically expressing human pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome-associated PSTPIP1 A230T mutant proteins. J Biol Chem. 2013;288:4594–601.PubMedPubMedCentralGoogle Scholar
  88. Wang H, Guo M, Shen S, et al. Variants in SELL, MRPS36P2, TP63, DDB2, CACNA1H, ADAM19, GNAI1, CDH13 and GABRG2 interact to confer risk of acne in Chinese population. J Dermatol. 2015;42:378–81.PubMedGoogle Scholar
  89. Wilkie AOM, Slaney SF, Oldridge M, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995;199:165–72.Google Scholar
  90. Williams C, Layton AM. Persistent acne in women: implications for the patient and for therapy. Am J Clin Dermatol. 2006;7:281–90.PubMedGoogle Scholar
  91. Wise CA, Gillum JD, Seidman CE, et al. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002;11:961–9.PubMedGoogle Scholar
  92. Xu SX, Wang HL, Fan X, et al. The familial risk of acne vulgaris in Chinese Hans—a case-control study. J Eur Acad Dermatol Venereol. 2007;21:602–5.PubMedGoogle Scholar
  93. Yang Z, Yu H, Cheng B, et al. Relationship between the CAG repeat polymorphism in the androgen receptor gene and acne in the Han ethnic group. Dermatology. 2009;218:302–6.PubMedGoogle Scholar
  94. Yang XY, Wu WJ, Yang C, et al. Association of HSD17B3 and HSD3B1 polymorphisms with acne vulgaris in Southwestern Han Chinese. Dermatology. 2013;227:202–8.PubMedGoogle Scholar
  95. Yang JK, Wu WJ, Qi J, et al. TNF-308 G/A polymorphism and risk of acne vulgaris: a meta-analysis. PLoS One. 2014a;9:e87806.PubMedPubMedCentralGoogle Scholar
  96. Yang JK, Wu WJ, He L, Zhang YP. Genotype-phenotype correlations in severe acne in a Han Chinese population. Dermatology. 2014b;229:210–4.PubMedGoogle Scholar
  97. Yaykasli KO, Turan H, Kaya E, Hatipoglu OF. Polymorphisms in the promoters of MMP-2 and TIMP-2 genes in patients with acne vulgaris. Int J Clin Exp Med. 2013;6:967–72.PubMedPubMedCentralGoogle Scholar
  98. Yentzer BA, Hick J, Reese EL, et al. Acne vulgaris in the United States: a descriptive epidemiology. Cutis. 2010;86:94–9.PubMedGoogle Scholar
  99. Yeon HB, Lindor NM, Seidman JG, Seidman CE. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet. 2000;66:1443–8.PubMedPubMedCentralGoogle Scholar
  100. Yiu ZZ, Madan V, Griffiths CE. Acne conglobata and adalimumab: use of tumour necrosis factor-α antagonists in treatment-resistant acne conglobata, and review of the literature. Clin Exp Dermatol. 2015;40:383–6.PubMedGoogle Scholar
  101. Younis S, Javed Q. The interleukin-6 and interleukin-1A gene promoter polymorphism is associated with the pathogenesis of acne vulgaris. Arch Dermatol Res. 2015;307:365–70.PubMedGoogle Scholar
  102. Younis S, Blumenberg M, Javed Q. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation. Arch Dermatol Res. 2016;308:229–37.PubMedGoogle Scholar
  103. Yu JW, Fernandes-Alnemri T, Datta P, et al. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cell. 2007;28:214–27.PubMedPubMedCentralGoogle Scholar
  104. Zhang M, Qureshi AA, Hunter DJ, Han J. A genome-wide association study of severe teenage acne in European Americans. Hum Genet. 2014;133:259–64.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gerd Plewig
    • 1
  • Bodo Melnik
    • 2
  • WenChieh Chen
    • 3
  1. 1.Department of Dermatology and AllergyLudwig-Maximilian-University MunichMunichGermany
  2. 2.Department of Dermatology, Environmental Medicine and Health TheoryUniversity of OsnabrückOsnabrückGermany
  3. 3.Department of Dermatology and AllergyTechnical University of MunichMunichGermany

Personalised recommendations