Investigation of four novel male androgenetic alopecia susceptibility loci: no association with female pattern hair loss

Springer Science and Business Media LLC - Tập 306 - Trang 413-418 - 2013
Rima Nuwaihyd1,2, Silke Redler1, Stefanie Heilmann1,3, Dmitriy Drichel4, Sabrina Wolf1, Pattie Birch5, Kathy Dobson5, Gerhard Lutz6, Kathrin A. Giehl7, Roland Kruse8, Rachid Tazi-Ahnini9, Sandra Hanneken10, Markus Böhm11, Anja Miesel12, Tobias Fischer12, Hans Wolff7, Tim Becker4,13, Natalie Garcia-Bartels2, Ulrike Blume-Peytavi2, Markus M. Nöthen1,3, Andrew G. Messenger5, Regina C. Betz1
1Institute of Human Genetics, University of Bonn, Bonn, Germany
2Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité-Universitätsmedizin Berlin, Berlin, Germany
3Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
4German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
5Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK
6Dermatological Practice, Hair and Nail, Wesseling, Wesseling, Germany
7Department of Dermatology, University of Munich, Munich, Germany
8Dermatological Practice, Paderborn, Paderborn, Germany
9Department of Infection and Immunity, University of Sheffield, Sheffield, UK
10Department of Dermatology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
11Laboratory for Neuroendocrinology of the Skin and Interdisciplinary Endocrinology, Department of Dermatology, University of Münster, Münster, Germany
12Department of Dermatology, University of Lübeck, Lübeck, Germany
13Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany

Tóm tắt

Female pattern hair loss (FPHL) is a common hair loss disorder in women and has a complex mode of inheritance. The etiopathogenesis of FPHL is largely unknown; however, it is hypothesized that FPHL and male pattern baldness [androgenetic alopecia (AGA)] share common genetic susceptibility alleles. Our recent findings indicate that the major AGA locus, an X-chromosome region containing the androgen receptor and the ectodysplasin A2 receptor (EDA2R) genes, may represent a common genetic factor underlying both early-onset FPHL and AGA. This gives further support for the widespread assumption of shared susceptibility loci for FPHL and AGA. However, we could not demonstrate association of further AGA risk loci, including 20p11, 1p36.22, 2q37.3, 7p21.1, 7q11.22, 17q21.31, and 18q21.1, with FPHL. Interestingly, a recent study identified four novel AGA risk loci in chromosomal regions 2q35, 3q25.1, 5q33.3, and 12p12.1. In particular, the 2q35 locus and its gene WNT10A point to an as-yet unknown involvement of the WNT signaling pathway in AGA. We hypothesized that the novel loci and thus also the WNT signaling may have a role in the etiopathogenesis of FPHL and therefore examined the role of these novel AGA risk loci in our FPHL samples comprising 440 German and 145 UK affected patients, 500 German unselected controls (blood donors), and 179 UK supercontrols. Patients and controls were genotyped for the top two single nucleotide polymorphisms at each of the four AGA loci. However, none of the genotyped variants displayed any significant association. In conclusion, the results of this study provide no support for the hypothesis that the novel AGA loci influence susceptibility to FPHL.

Tài liệu tham khảo

Andl T, Reddy ST, Gaddapara T, Millar SE (2002) WNT signals are required for the initiation of hair follicle development. Dev Cell 2:643–653 Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19:179–192 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 Bravo DT, Yang YL, Kuchenbecker K, Hung MS, Xu Z, Jablons DM, You L (2013) Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer. BMC Cancer 13:316 Brockschmidt FF, Hillmer AM, Eigelshoven S et al (2010) Fine mapping of the human AR/EDA2R locus in androgenetic alopecia. Br J Dermatol 162:899–903 Gan DC, Sinclair RD (2005) Prevalence of male and female pattern hair loss in Maryborough. J Investig Dermatol Symp Proc 10:184–189 Headington JT (1984) Transverse microscopic anatomy of the human scalp. A basis for a morphometric approach to disorders of the hair follicle. Arch Dermatol 120:449–456 Heilmann S, Kiefer AK, Fricker N et al (2013) Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology. J Invest Dermatol 133:1489–1496 Küster W, Happle R (1984) The inheritance of common baldness: two B or not two B? J Am Acad Dermatol 11:921–926 Li R, Brockschmidt FF, Kiefer AK et al (2012) Six novel susceptibility loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genet 8:e1002746 Ludwig E (1977) Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol 97:247–254 Millar SE, Willert K, Salinas PC, Roelink H, Nusse R, Sussman DJ, Barsh GS (1999) WNT signaling in the control of hair growth and structure. Dev Biol 207:133–149 Norwood OT (2001) Incidence of female androgenetic alopecia (female pattern alopecia). Dermatol Surg 27:53–54 Nyholt DR, Gillespie NA, Heath AC, Martin NG (2003) Genetic basis of male pattern baldness. J Invest Dermatol 121:1561–1564 Armitage P (1955) Tests for linear trends in proportions and frequencies. Biometrics 11(3):375–386 Reddy S, Andl T, Bagasra A, Lu MM, Epstein DJ, Morrisey EE, Millar SE (2001) Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of sonic hedgehog in hair follicle morphogenesis. Mech Dev 107:69–82 Redler S, Birch MP, Drichel D et al (2011) Investigation of variants of the aromatase gene (CYP19A1) in female pattern hair loss. Br J Dermatol 165:703–705 Redler S, Brockschmidt FF, Tazi-Ahnini R et al (2012) Investigation of the male pattern baldness major genetic susceptibility loci AR/EDA2R and 20p11 in female pattern hair loss. Br J Dermatol 166:1314–1318 Redler S, Dobson K, Drichel D, Heilmann S, wolf S, Brockschmidt FF, Tazi-Ahnini R, Birch P et al (2013) Investigation of six novel loci for male androgenetic alopecia in women with female pattern hair loss. J Dermatol Sci 72(2):186–188 Redler S, Tazi-Ahnini R, Drichel D et al (2012) Selected variants of the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2 and the sex steroid hormone receptors ESR1, ESR2 and PGR: no association with female pattern hair loss identified. Exp Dermatol 21:390–393 Riedel-Baima B, Riedel A (2008) Female pattern hair loss may be triggered by low oestrogen to androgen ratio. Endocr Regul 42:13–16 Sinclair R, Jolley D, Mallari R, Magee J (2004) The reliability of horizontally sectioned scalp biopsies in the diagnosis of chronic diffuse telogen hair loss in women. J Am Acad Dermatol 51:189–199 Smith MA, Wells RS (1964) Male-type alopecia, alopecia areata, and normal hair in women; family histories. Arch Dermatol 89:95–98 Vexiau P, Chaspoux C, Boudou P, Fiet J, Abramovici Y, Rueda MJ, Hardy N, Reygagne P (2000) Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism. Arch Dermatol Res 292:598–604 Wang HY, Malbon CC (2004) Wnt-frizzled signaling to G-protein-coupled effectors. Cell Mol Life Sci 61:69–75 Yip L, Zaloumis S, Irwin D, Severi G, Hopper J, Giles G, Harrap S, Sinclair R, Ellis J (2012) Association analysis of oestrogen receptor beta gene (ESR2) polymorphisms with female pattern hair loss. Br J Dermatol 166:1131–1134 Yip L, Zaloumis S, Irwin D, Severi G, Hopper J, Giles G, Harrap S, Sinclair R, Ellis J (2009) Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. Br J Dermatol 161:289–294