A Synonymous Polymorphism of APCDD1 Affects Translation Efficacy and is Associated with Androgenic Alopecia

The APCDD1 (adenomatosis polyposis coli down-regulated 1) gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients (n = 210) with androgenic alopecia and 98 controls were investigated. SNPs (Single nucleotide polymorphisms) in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c.1781C/T, p.L476L SNP (rs3185480) of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote (CI 0.933-13.125; nominal regression P = 0.063) and heterozygote (CI 1.086-7.217; nominal regression P = 0.033) carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDD1 protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon (CTC) to a rare codon (CTT), which might influence translation efficiency and, thus, APCDD1 protein level.