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

作     者：Nikoletta Nagy Katalin Farkas Agnes Kinyo Barbara Fazekas Kornelia Szabo Edit Kollar Balazs Sztano Angela Meszes Dora Beke Lajos Kemeny Laszlo Royo Marta Szell 

作者机构：Department of Medical Genetics University of Szeged Szeged 6720 Hungary Department of Dermatology andAllergology University ofSzeged Szeged 6720 Hungary Dermatological Research Group Hungarian Academy of Sciences Szeged 6720 Hungary Department of Rhino-Laryngology and Head-Neck Surgery University ofSzeged Szeged 6720 Hungary 

出 版 物：《Journal of Life Sciences》 (生命科学（英文版）)

年 卷 期：2014年第8卷第2期

页      面：106-114页

学科分类：07[理学] 081203[工学-计算机应用技术] 08[工学] 0835[工学-软件工程] 0713[理学-生态学] 0812[工学-计算机科学与技术（可授工学、理学学位）] 

主　　题：Adenomatosis polyposis coli down-regulated 1 gene hereditary hypotrichosis simplex androgenic alopecia,polymorphism synonymous translation efficacy preferable codon. 

摘      要：The APCDDI （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 APCDDI 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, APCDDI protein level.