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Keywords:

  • androgen receptor gene;
  • androgenetic alopecia;
  • CAG repeat;
  • Kennedy disease;
  • spinal and bulbar muscular atrophy

Summary

Background  Spinal and bulbar muscular atrophy or Kennedy disease (KD) is an X-linked neurodegenerative disease caused by an expansion of a polymorphic tandem CAG repeat within the androgen receptor (AR) gene on chromosomal locus Xq11-q12. The CAG repeat region encodes a polyglutamine tract that, when expanded to above 40 in number, results in KD, a neurodegenerative disease primarily targeting lower motor neurones. KD is also associated with partial androgen insensitivity due to loss of receptor function. Degree of expansion of this repeat region, located in the first exon, is correlated with age at onset and disease severity. Androgenetic alopecia (AGA) is a polygenic trait also associated with functional polymorphism of the AR gene.

Objectives  To test whether partial loss of function in the AR gene associated with CAG polymorphism reduces the risk of AGA in affected men.

Methods  Members of the Kennedy’s Disease Association, an American-based support group, were invited to participate in an online survey to determine the age-related prevalence of AGA among men affected by KD. Data from 115 respondents with KD were compared with data from 654 white men of European descent in Maryborough, Australia.

Results  The mean AGA score for men with KD was 1·64 (95% confidence interval, CI 1·41–1·87). The mean score for men in Maryborough was 2·82 (95% CI 2·71–2·93). The difference between the means was highly significant (< 0·001), indicating thicker hair among the KD cohort. Treating AGA score as a continuous variable we found age to be highly significantly related to AGA score in men from Maryborough (< 0·001) but not among men affected by KD (= 0·90).

Conclusions  Men with KD have a reduced risk of AGA, likely to be due to a functional alteration in the AR caused by the polyglutamine expansion.