title: The hairless gene in androgenetic alopecia: results of a systematic mutation screening and a family-based association approach.
abstract: BACKGROUND
  Genetic disposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as androgenetic alopecia (AGA). The genetic factors contributing to AGA are currently unknown. The human hairless gene (HR) has recently been cloned and mutations have been reported in families with autosomal recessive universal congenital alopecia and papular atrichia. The main feature of these disorders is persistent complete absence of hair at or shortly after birth. This suggests that HR is essential and specific for the development of hair.
  
  
  OBJECTIVE
  To test the hypothesis that HR may be involved in AGA.
  
  
  METHODS
  We systematically screened HR for genetic variability by means of single-strand conformation analysis (SSCA) in 46 unrelated men with AGA. To test for an involvement of HR in the development of AGA, seven common variants were genotyped in 61 families with 93 affected offspring. The results were analysed with the transmission/disequilibrium test (TDT).
  
  
  RESULTS
  SSCA showed 15 single nucleotide substitutions: eight missense mutations, four silent mutations and three mutations in exon-flanking intronic sequences. TDT results showed a marginally significant association between AGA and variants 3379-29G/T (P = 0.024) and 2611-68C/T (P = 0.047). These results, however, did not remain significant after applying the conservative Bonferroni correction for multiple testing.
  
  
  CONCLUSIONS
  Our results do not provide evidence for a strong involvement of HR in the development of AGA, although a minor role cannot be fully excluded.
authors.affiliation: Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: R
authors.initials: R
authors.lastname: Kruse
authors.forename: F
authors.initials: F
authors.lastname: Macciardi
authors.forename: U
authors.initials: U
authors.lastname: Heyn
authors.forename: R C
authors.initials: RC
authors.lastname: Betz
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: P
authors.initials: P
authors.lastname: Propping
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: S
authors.initials: S
authors.lastname: Cichon
mesh_terms: D000328:Adult; D000483:Alleles; D000505:Alopecia / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D017931:DNA Primers; C490267:HR protein, human; D011506:Proteins; D014157:Transcription Factors