#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia


Autoři: Arang Rhie aff001;  Ho-Young Son aff001;  Soo Jung Kwak aff001;  Seungbok Lee aff001;  Dong Young Kim aff005;  Bark-Lynn Lew aff008;  Woo-Young Sim aff008;  Jeong-Sun Seo aff001;  Ohsang Kwon aff005;  Jong-Il Kim aff001;  Seong Jin Jo aff005
Působiště autorů: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea aff001;  Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America aff002;  Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea aff003;  Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea aff004;  Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea aff005;  Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea aff006;  Institute of Human-Environmental Interface Biology, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea aff007;  Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea aff008
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222533

Souhrn

Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher’s exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.

Klíčová slova:

Biology and life sciences – Anatomy – Integumentary system – Hair – Skin – Hair follicles – Genetics – Heredity – Genetic mapping – Variant genotypes – Molecular genetics – Genetic loci – Alleles – Molecular biology – Biochemistry – Hormones – Androgens – Medicine and health sciences – Pharmacology – Pharmacokinetics – Drug metabolism – Research and analysis methods – Mathematical and statistical techniques – Statistical methods – Regression analysis – Physical sciences – Mathematics – Statistics – Linear regression analysis


Zdroje

1. Sinclair R. Male pattern androgenetic alopecia. BMJ. 1998;317(7162):865–9. doi: 10.1136/bmj.317.7162.865 9748188; PubMed Central PMCID: PMC1113949.

2. Whiting DA. Male pattern hair loss: current understanding. Int J Dermatol. 1998;37(8):561–6. doi: 10.1046/j.1365-4362.1998.00542.x 9731996

3. Norwood OT. Male pattern baldness: classification and incidence. South Med J. 1975;68(11):1359–65. doi: 10.1097/00007611-197511000-00009 1188424.

4. Nyholt DR, Gillespie NA, Heath AC, Martin NG. Genetic basis of male pattern baldness. J Invest Dermatol. 2003;121(6):1561–4. doi: 10.1111/j.1523-1747.2003.12615.x 14675213

5. Ellis JA, Stebbing M, Harrap SB. Polymorphism of the androgen receptor gene is associated with male pattern baldness. J Invest Dermatol. 2001;116(3):452–5. doi: 10.1046/j.1523-1747.2001.01261.x WOS:000167222200014. 11231320

6. Hayes VM, Severi G, Eggleton SA, Padilla EJD, Southey MC, Sutherland RL, et al. The E211 G > A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. Cancer Epidem Biomar. 2005;14(4):993–6. doi: 10.1158/1055-9965.Epi-04-0778 WOS:000228351300038. 15824176

7. Hillmer AM, Hanneken S, Ritzmann S, Becker T, Freudenberg J, Brockschmidt FF, et al. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am J Hum Genet. 2005;77(1):140–8. doi: 10.1086/431425 15902657

8. Levy-Nissenbaum E, Bar-Natan M, Frydman M, Pras E. Confirmation of the association between male pattern baldness and the androgen receptor gene. Eur J Dermatol. 2005;15(5):339–40. WOS:000232392300005. 16172040

9. Richards JB, Yuan X, Geller F, Waterworth D, Bataille V, Glass D, et al. Male-pattern baldness susceptibility locus at 20p11. Nat Genet. 2008;40(11):1282–4. doi: 10.1038/ng.255 WOS:000260501500017. 18849991

10. Hillmer AM, Flaquer A, Hanneken S, Eigelshoven S, Kortum AK, Brockschmidt FF, et al. Genome-wide scan and fine-mapping linkage study of androgenetic alopecia reveals a locus on chromosome 3q26. Am J Hum Genet. 2008;82(3):737–43. doi: 10.1016/j.ajhg.2007.11.014 18304493; PubMed Central PMCID: PMC2427264.

11. Li R, Brockschmidt FF, Kiefer AK, Stefansson H, Nyholt DR, Song K, et al. Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genet. 2012;8(5):e1002746. Epub 2012/06/14. doi: 10.1371/journal.pgen.1002746 22693459; PubMed Central PMCID: PMC3364959.

12. Heilmann S, Kiefer AK, Fricker N, Drichel D, Hillmer AM, Herold C, et al. Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology. J Invest Dermatol. 2013;133(6):1489–96. Epub 2013/01/30. doi: 10.1038/jid.2013.43 23358095.

13. Brockschmidt FF, Heilmann S, Ellis JA, Eigelshoven S, Hanneken S, Herold C, et al. Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness. Br. 2011;165(6):1293–302. Epub 2011/10/29. doi: 10.1111/j.1365-2133.2011.10708.x 22032556.

14. Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39(4):578–89.

15. Eun HC, Kwon OS, Yeon JH, Shin HS, Kim BY, Ro BI, et al. Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: A randomized, double-blind, placebo-controlled, phase III study. J Am Acad Dermatol. 2010;63(2):252–8. doi: 10.1016/j.jaad.2009.09.018 WOS:000280252100008. 20605255

16. Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, et al. The importance of dual 5α-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol. 2006;55(6):1014–23. doi: 10.1016/j.jaad.2006.05.007 17110217

17. Prodi DA, Pirastu N, Maninchedda G, Sassu A, Picciau A, Palmas MA, et al. EDA2R is associated with androgenetic alopecia. J Invest Dermatol. 2008;128(9):2268–70. doi: 10.1038/jid.2008.60 18385763

18. Hillmer AM, Freudenberg J, Myles S, Herms S, Tang K, Hughes DA, et al. Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness. Hum Genet. 2009;126(2):255–64. doi: 10.1007/s00439-009-0668-z 19373488

19. Hayes VM, Severi G, Padilla EJ, Morris HA, Tilley WD, Southey MC, et al. 5α−Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia. Int J Cancer. 2007;120(4):776–80. doi: 10.1002/ijc.22408 17136762

20. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9(4):357–9. doi: 10.1038/nmeth.1923 22388286; PubMed Central PMCID: PMC3322381.

21. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297–303. doi: 10.1101/gr.107524.110 20644199; PubMed Central PMCID: PMC2928508.

22. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43(5):491–8. doi: 10.1038/ng.806 WOS:000289972600023. 21478889

23. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164–e. doi: 10.1093/nar/gkq603 20601685

24. Krumm N, Sudmant PH, Ko A, O'Roak BJ, Malig M, Coe BP, et al. Copy number variation detection and genotyping from exome sequence data. Genome Res. 2012;22(8):1525–32. doi: 10.1101/gr.138115.112 22585873; PubMed Central PMCID: PMC3409265.

25. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75. doi: 10.1086/519795 17701901; PubMed Central PMCID: PMC1950838.

26. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263–5. doi: 10.1093/bioinformatics/bth457 15297300.

27. Liu JZ, McRae AF, Nyholt DR, Medland SE, Wray NR, Brown KM, et al. A versatile gene-based test for genome-wide association studies. Am J Hum Genet. 2010;87(1):139–45. doi: 10.1016/j.ajhg.2010.06.009 20598278; PubMed Central PMCID: PMC2896770.

28. Moore JH, Gilbert JC, Tsai CT, Chiang FT, Holden T, Barney N, et al. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol. 2006;241(2):252–61. doi: 10.1016/j.jtbi.2005.11.036 16457852.

29. Chetyrkin SV, Belyaeva OV, Gough WH, Kedishvili NY. Characterization of a Novel Type of Human Microsomal 3α-Hydroxysteroid Dehydrogenase. J Biol Chem. 2001;276(25):22278–86. doi: 10.1074/jbc.M102076200 11294878

30. Everts HB, Silva KA, Montgomery S, Suo L, Menser M, Valet AS, et al. Retinoid metabolism is altered in human and mouse cicatricial alopecia. J Invest Dermatol. 2013;133(2):325–33. doi: 10.1038/jid.2012.393 23096705; PubMed Central PMCID: PMC3546159.

31. Markova NG, Pinkas-Sarafova A, Karaman-Jurukovska N, Jurukovski V, Simon M. Expression pattern and biochemical characteristics of a major epidermal retinol dehydrogenase. Mol Genet Metab. 2003;78(2):119–35. 12618084.

32. Rexer BN, Ong DE. A novel short-chain alcohol dehydrogenase from rats with retinol dehydrogenase activity, cyclically expressed in uterine epithelium. Biol Reprod. 2002;67(5):1555–64. doi: 10.1095/biolreprod.102.007021 12390888.

33. Soref CM, Di Y-P, Hayden L, Zhao YH, Satre MA, Wu R. Characterization of a novel airway epithelial cell-specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol. J Biol Chem. 2001;276(26):24194–202. doi: 10.1074/jbc.M100332200 11304534

34. Napoli JL. Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta. 1999;1440(2):139–62.

35. Everts HB, Sundberg JP, King LE Jr., Ong DE. Immunolocalization of enzymes, binding proteins, and receptors sufficient for retinoic acid synthesis and signaling during the hair cycle. J Invest Dermatol. 2007;127(7):1593–604. doi: 10.1038/sj.jid.5700753 17363914.

36. Everts HB, King LE Jr., Sundberg JP, Ong DE. Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation. J Invest Dermatol. 2004;123(2):258–63. doi: 10.1111/j.0022-202X.2004.23223.x 15245423.

37. Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. J Lipid Res. 2002;43(11):1773–808. doi: 10.1194/jlr.r100015-jlr200 12401878.

38. Roos TC, Jugert FK, Merk HF, Bickers DR. Retinoid metabolism in the skin. Pharmacol Rev. 1998;50(2):315–33. 9647871.

39. Loriè EP, Chamcheu JC, Vahlquist A, Törmä H. Both all-trans retinoic acid and cytochrome P450 (CYP26) inhibitors affect the expression of vitamin A metabolizing enzymes and retinoid biomarkers in organotypic epidermis. Arch Dermatol Res. 2009;301(7):475–85. doi: 10.1007/s00403-009-0937-7 19294396

40. Pavez Lorie E, Cools M, Borgers M, Wouters L, Shroot B, Hagforsen E, et al. Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid-regulated genes in normal human epidermis. Br. 2009;160(1):26–36. doi: 10.1111/j.1365-2133.2008.08895.x 19016711.

41. Pavez Lorie E, Li H, Vahlquist A, Torma H. The involvement of cytochrome p450 (CYP) 26 in the retinoic acid metabolism of human epidermal keratinocytes. Biochim Biophys Acta. 2009;1791(3):220–8. Epub 2009/01/28. doi: 10.1016/j.bbalip.2008.12.004 19171200.

42. White JA, Ramshaw H, Taimi M, Stangle W, Zhang AQ, Everingham S, et al. Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism. P Natl Acad Sci USA. 2000;97(12):6403–8. doi: 10.1073/pnas.120161397 WOS:000087526300033. 10823918

43. Ohnemus U, Uenalan M, Inzunza J, Gustafsson JÅ, Paus R. The hair follicle as an estrogen target and source. Endocr Rev. 2006;27(6):677–706. doi: 10.1210/er.2006-0020 16877675

44. Oh H-S, Smart RC. An estrogen receptor pathway regulates the telogen-anagen hair follicle transition and influences epidermal cell proliferation. P Natl Acad Sci USA. 1996;93(22):12525–30.

45. Ohnemus U, Unalan M, Handjiski B, Paus R. Topical estrogen accelerates hair regrowth in mice after chemotherapy-induced alopecia by favoring the dystrophic catagen response pathway to damage. J Invest Dermatol. 2004;122(1):7–13. doi: 10.1046/j.0022-202X.2003.22120.x 14962083.


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#