F25 ANDROGENETIC ALOPECIA: RELATIONSHIP TO GENETIC VARIABILITY IN THE HUMAN HAIRLESS GENE

¹Kruse R., ²Hillmer A. M., ²Cichon S., ³Macciardi F., ²Nöthen M. M.; ¹Department of Dermatology, Heinrich-Heine University, Düsseldorf, Germany; ²Institute of Human Genetics, Rheinische Freidrich-Wilhelms University, Bonn, Germany; ³Unit of Biostatistics and Genetic Epidemiology, University of Toronto, Canada

Recent studies suggest that the human hairless gene (HR) is essential and specific for the development of hair. To test the hypothesis that genetic variants of HR contribute to the development of androgenetic areata (AGA), we systematically screened the HR gene for genetic variability by means of single strand conformation analysis (SSCA) in 46 unrelated men with AGA. We detected 15 single nucleotide poymorphisms including eight missense mutations (205C^®T, 1010G^®A, 1190G^®A, 1577T^®C, 1727C^®T, 1772A^®G, 1859G^®A, 3064A^®G) and seven silent mutations (1305T^®C, 2370T^®C, 2611-68C^®T, 2611-52T^®C, 3234C^®G, 3339C^®A, 3379-29G^®T). We tested seven common variants in a sample of 93 trio families (affected male plus parents) for association with AGA using the transmission disequilibrium test. A significant association was found between AGA and variant 3379-29G^®T (p=0,024). Because the 3379-29G^®T substitution is probably without functional relevance itself, our results suggest the presence of a yet undetected mutation predisposing to AGA in linkage disequilibrium with 3379-29^®T. Definite conclusions, however, require replication of the finding in independent samples.