Polymorphisms in Genes Involved in Steroidogenesis in the Development of Severe Acne

Alexander G. Rumyantsev, Olga M. Dеmina

International Journal of Biomedicine. 2021;11(3):275-280.
DOI: 10.21103/Article11(3)_OA4
Originally published September 9, 2021


Background: Acne is a multifactorial disease, in the pathogenesis of which one of the leading factors is the excessive effect of androgens on the hair follicles (HFs) and sebaceous glands (SGs), along with hypersecretion of sebum, pathological follicular hyperkeratosis and an inflammatory response. The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. The aim of this study was to determine SNPs within 3 genes involved in steroidogenesis (MVK, ARPC1B, and CA2) in patients with severe acne.
Methods and Results: The study included 70 patients (42 men and 28 women) aged between 15 and 46 years (the median age - 22.1 years). The main group (MG) included 50 patients (29 men and 21 women) with severe acne. The control group (CG) consisted of 20 apparently healthy individuals (13 men and 7 women). Molecular-genetic diagnostics was carried out by the method of high-throughput DNA sequencing (next-generation sequencing). Our study showed that severe acne is associated with 12 polymorphic loci of the MVK gene (4 SNPs in exons and 8 SNPs in introns), 7 SNPs of the ARPC1B gene (2 SNPs in exons and 5 SNPs in introns), and 9 SNPs of the CA2 gene (3 SNPs in exons and 6 SNPs in introns).
Conclusion: The revealed features of the SNPs within the MVK, ARPC1B, and CA2 genes in patients with severe acne probably indicate a hereditary determination of steroidogenesis in acne.

acne • hair follicle • sebaceous gland • steroidogenesis • single nucleotide polymorphism
  1. New MI. An update of congenital adrenal hyperplasia. Ann N Y Acad Sci. 2004 Dec;1038:14-43. doi: 10.1196/annals.1315.009.
  2. Chen WC, Zouboulis CC. Hormones and the pilosebaceous unit. Dermatoendocrinol. 2009 Mar;1(2):81-6. doi: 10.4161/derm.1.2.8354.
  3. Orfanos CE, Adler YD, Zouboulis CC. The SAHA syndrome. Horm Res. 2000;54(5-6):251-8. doi: 10.1159/000053267.
  4. Imperato-McGinley J. 5alpha-reductase-2 deficiency and complete androgen insensitivity: lessons from nature. Adv Exp Med Biol. 2002;511:121-31; discussion 131-4. doi: 10.1007/978-1-4615-0621-8_8. 
  5. Eklöf AC, Thurelius AM, Garle M, Rane A, Sjöqvist F. The anti-doping hot-line, a means to capture the abuse of doping agents in the Swedish society and a new service function in clinical pharmacology. Eur J Clin Pharmacol. 2003 Nov;59(8-9):571-7. doi: 10.1007/s00228-003-0633-z. 
  6. Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol. 2005 Mar;141(3):333-8. doi: 10.1001/archderm.141.3.333.
  7. Inoue T, Miki Y, Kakuo S, Hachiya A, Kitahara T, Aiba S, Zouboulis CC, Sasano H. Expression of steroidogenic enzymes in human sebaceous glands. J Endocrinol. 2014 Sep;222(3):301-12. doi: 10.1530/JOE-14-0323. 
  8. Nagy I, Pivarcsi A, Kis K, Koreck A, Bodai L, McDowell A, Seltmann H, Patrick S, Zouboulis CC, Kemény L. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes Infect. 2006 Jul;8(8):2195-205. doi: 10.1016/j.micinf.2006.04.001. 
  9. Szöllősi AG, Oláh A, Bíró T, Tóth BI. Recent advances in the endocrinology of the sebaceous gland. Dermatoendocrinol. 2018 Jan 23;9(1):e1361576. doi: 10.1080/19381980.2017.1361576. 
  10. Alestas T, Ganceviciene R, Fimmel S, Müller-Decker K, Zouboulis CC. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med (Berl). 2006 Jan;84(1):75-87. doi: 10.1007/s00109-005-0715-8. 
  11. Barrault C, Garnier J, Pedretti N, Cordier-Dirikoc S, Ratineau E, Deguercy A, Bernard FX. Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor. J Steroid Biochem Mol Biol. 2015 Aug;152:34-44. doi: 10.1016/j.jsbmb.2015.04.005. 
  12. Dajnoki Z, Béke G, Kapitány A, Mócsai G, Gáspár K, Rühl R, Hendrik Z, Juhász I, Zouboulis CC, Bácsi A, Bíró T, Törőcsik D, Szegedi A. Sebaceous Gland-Rich Skin Is Characterized by TSLP Expression and Distinct Immune Surveillance Which Is Disturbed in Rosacea. J Invest Dermatol. 2017 May;137(5):1114-1125. doi: 10.1016/j.jid.2016.12.025.
  13. Makrantonaki E, Zouboulis CC. Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes. Br J Dermatol. 2007 Mar;156(3):428-32. doi: 10.1111/j.1365-2133.2006.07671.x. 
  14. Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000 Aug;21(4):363-92. doi: 10.1210/edrv.21.4.0404. 
  15. Wei B, Qu L, Zhu H, Xiao T, Wei HC, Chen HD, He C. Higher 17α-hydroxyprogesterone levels aggravated the severity of male adolescent acne in Northeast China. Dermatology. 2014;229(4):359-62. doi: 10.1159/000365656.
  16. Lam C, Zaenglein AL. Contraceptive use in acne. Clin Dermatol. 2014 Jul-Aug;32(4):502-15. doi: 10.1016/j.clindermatol.2014.05.002. 
  17. Makrantonaki E, Vogel K, Fimmel S, Oeff M, Seltmann H, Zouboulis CC. Interplay of IGF-I and 17beta-estradiol at age-specific levels in human sebocytes and fibroblasts in vitro. Exp Gerontol. 2008 Oct;43(10):939-46. doi: 10.1016/j.exger.2008.07.005. 
  18.  Szabó K, Kemény L. Studying the genetic predisposing factors in the pathogenesis of acne vulgaris. Hum Immunol. 2011 Sep;72(9):766-73. doi: 10.1016/j.humimm.2011.05.012.
  19. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012 Jan 28;379(9813):361-72. doi: 10.1016/S0140-6736(11)60321-8. Epub 2011 Aug 29. Erratum in: Lancet. 2012 Jan 28;379(9813):314. 
  20. He L, Wu WJ, Yang JK, Cheng H, Zuo XB, Lai W, et al. Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne. Nat Commun. 2014;5:2870. doi: 10.1038/ncomms3870. 
  21. Demirkan S, Sayın DB, Gündüz Ö. CAG polymorphism in the androgen receptor gene in women may be associated with nodulocystic acne. Postepy Dermatol Alergol. 2019 Apr;36(2):173-176. doi: 10.5114/ada.2019.84592. 

Download Article
Received July 4, 2021.
Accepted August 13, 2021.
©2021 International Medical Research and Development Corporation.