Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciences0869-60472414-3545"Paediatrician" Publishers LLC114110.15690/vramn1141Research ArticleThe Value of Genetic and Non-Genetic Factors in the Emergence and in the Development of Androgenetic Alopecia in Men: Multifactor AnalysisKondrakhinaIrina N.<p class="MsoNormal"><span lang="EN-US" style="mso-ansi-language: EN-US;">MD, PhD</span></p>
<p class="MsoNormal"> </p>kondrakhina77@gmail.comhttps://orcid.org/0000-0003-3662-9954VerbenkoDmitry A.<p class="MsoNormal"><span lang="EN-US" style="mso-ansi-language: EN-US;">PhD</span></p>verbenko@gmail.comhttps://orcid.org/0000-0002-1104-7694ZatevalovAlexander M.<p class="MsoNormal"><span lang="EN-US" style="mso-ansi-language: EN-US;">PhD</span></p>zatevalov@mail.ruhttps://orcid.org/0000-0002-1460-4361KubanovAlexey A.<p class="MsoNormal"><span lang="EN-US" style="mso-ansi-language: EN-US;">MD, PhD, Professor</span></p>kubanov@list.ruhttps://orcid.org/0000-0002-7625-0503DeryabinDmitrij G.<p class="MsoNormal"><span lang="EN-US" style="mso-ansi-language: EN-US;">MD, PhD, Professor</span></p>dgderyabin@yandex.ruhttps://orcid.org/0000-0002-2495-6694State Research Center of Dermatovenereology and CosmetologyG.N. Gabrichevsky Research Institute for Epidemiology and Microbiology270720197431671751705201925062019Copyright © 2019, "Paediatrician" Publishers LLC2019<p><strong>Background</strong>: Among pathological hair loss conditions in men the androgenic alopecia (L64 according to ICD-10) has been the most common diagnosed. However, the reasons of the occurrence and development of the disease remain incompletely clarified, that determines the difficulties of personalized therapy.</p>
<p><strong>Aims</strong>: To analyze both genetic and non-genetic factors involved in the pathogenesis of androgenic alopecia in men, and to create personalized multifactorial model for description of individual causes of the disease.</p>
<p><strong>Materials and methods</strong>: The genetic predisposition to androgenic alopecia was estimated by the set of SNP rs929626, rs5919324, rs1998076, rs12565727 and rs756853, analyzed by mini-sequencing. The non-genetic factors included: hormones and metabolic markers, trace elements, and vitamins. Two-stage model creation of androgenic alopecia occurrence and development was carried out using a neural network (for genetic factors) followed by step-by-step linear discriminate analysis (for non-genetic factors).</p>
<p><strong>Results</strong>: The case-control study included 50 men revealing IIV stages of androgenic alopecia (according to Norwood-Hamilton classification) and 25 healthy volunteers relevant in their age and origin. The analysis of each SNP separately did not show significant differences between these groups, while SNP joint consideration in neural network model made it possible to assess the genetic predisposition to androgenic alopecia, as well as to divide the low and high genetic risk subgroups. A large number of significant non-genetic factors, including elevated levels of dihydrotestosterone, 17-OH-progesterone, insulin, and deficiency of Mg, Cu, Zn, Se, vitamins D, E, folic acid was shown in low genetic risk subgroup. In turn, in the high genetic risk subgroup the set of significant non-genetic factors was limited to metabolic and micronutrient disorders only. These data were used for the multifactorial model showing 81.285.1% accuracy being the most effective in early (III) stages of androgenic alopecia.</p>
<p><strong>Conclusions</strong>: The different influence of non-genetic factors in patients with low and high genetic risk of androgenic alopecia has been revealed. The integral factors consideration in the proposed two-stage multifactorial model identifies individual causes of the disease and gives the chance for the development of personalized therapy of androgenic alopecia in men.</p>androgenic alopeciagenetic predispositiontrace elementvitaminhormonestatistical modelандрогенная алопециягенетические факторынегенетические факторымногопараметрическая модель[Randall VA. Molecular basis of androgenetic alopecia. In: Trüeb RM, Tobin DJ (eds). Aging hair. Springer, Berlin; 2010. Pp. 9–24.][Lolli F, Pallotti F, Rossi A, et al. Androgenetic alopecia: a review. Endocrine. 2017;57(1):9–17. doi: 10.1007/s12020-017-1280-y.][Pirastu N, Joshi PK, de Vries PS, et al. GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk. Nat Commun. 2017;8(1):1584. doi: 10.1038/s41467-017-01490-8.][Yap CX, Sidorenko J, Wu Y, et al. Dissection of genetic variation and evidence for pleiotropy in male pattern baldness. Nat Commun. 2018;9(1):5407. doi: 10.1038/s41467-018-07862-y.][Marcińska M, Pośpiech E, Abidi S, et al. Evaluation of DNA variants associated with androgenetic alopecia and their potential to predict male pattern baldness. PLoS One. 2015;10(5):e0127852. doi: 10.1371/journal.pone.0127852.][Kondrakhina IN, Verbenko DA, Zatevalov AM, et al. SNP variation in male pattern hair loss in Russians with different dihydrotestosterone levels. Meta Gene. 2019;19(2):219−224. doi: 10.1016/j.mgene.2018.12.011.][Sánchez P, Serrano-Falcón C, Torres JM, et al. 5α-Reductase isozymes and aromatase mRNA levels in plucked hair from young women with female pattern hair loss. Arch Dermatol Res. 2018;310(1):77–83. doi: 10.1007/s00403-017-1798-0.][Jin W, Zheng H, Shan B, Wu Y. Changes of serum trace elements level in patients with alopecia areata: a meta-analysis. J Dermatol. 2017;44(5):588–591. doi: 10.1111/1346-8138.13705.][Fawzi MM, Mahmoud SB, Ahmed SF, et al. Assessment of vitamin D receptors in alopecia areata and androgenetic alopecia. J Cosmet Dermatol. 2016;15(4):318–323. doi: 10.1111/jocd.12224.][Mahmood L. The metabolic processes of folic acid and Vitamin B12 deficiency. J Health Res Rev. 2014;1(1):5−9. doi: 10.4103/2394-2010.143318.][Lie C, Liew CF, Oon HH. Alopecia and the metabolic syndrome. Clin Dermatol. 2018;36(1):54–61. doi: 10.1016/j.clindermatol.2017.09.009.][STATISTICA help [Internet], 2019. STATISTICA automated neuronal networks overviews ― network types. The multilayer perceptron neural networks. [cited 2019 Apr 11] Available from: http://documentation.statsoft.com/STATISTICAHelp.aspx?path=SANN/Overview/SANNNeuralNetworksAnOverview.][Panda S. A review on regulation of gene in eukaryotes. Int J Bioassays. 2016;5(8):4729–4732. doi: 10.21746/ijbio.2016.08.001.][Skalnaya MG. Copper deficiency a new reason of androgenetic alopecia? In: Pharmacology and nutritional intervention in the treatment of disease. Chapter 17. 2014. Рр. 337–348. doi: 10.5772/58416.][Rajendrasingh JR. Role of non-androgenic factors in hair loss and hair regrowth. J Cosmo Trichol. 2017;3:118. doi: 10.4172/2471-9323.1000118.][Madaan A, Verma R, Singh AT, Jaggi M. Review of hair follicle dermal papilla cells as in vitro screening model for hair growth. Int J Cosmet Sci. 2018;40(5):429–450. doi: 10.1111/ics.12489.][Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A. The role of vitamins and minerals in hair loss: a review. Dermatol Ther (Heidelb). 2019;9(1):51–70. doi: 10.1007/s13555-018-0278-6.][Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr. 2012;3(1):21–38. doi: 10.3945/an.111.000992.][Hochfeld LM, Anhalt T, Reinbold CS, et al. Expression profiling and bioinformatic analyses suggest new target genes and pathways for human hair follicle related microRNAs. BMC Dermatol. 2017;17(1):3. doi: 10.1186/s12895-017-0054-9.]