title: Large-scale analysis reveals a functional single-nucleotide polymorphism in the 5'-flanking region of PRDM16 gene associated with lean body mass.
abstract: Genetic factors are important for the development of sarcopenia, a geriatric disorder characterized by low lean body mass. The aim of this study was to search for novel genes that regulate lean body mass in humans. We performed a large-scale search for 250K single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) using SNP arrays in 1081 Japanese postmenopausal women. We focused on an SNP (rs12409277) located in the 5'-flanking region of the PRDM16 (PRD1-BF-1-RIZ1 homologous domain containing protein 16) gene that showed a significant P value in our screening. We demonstrated that PRDM16 gene polymorphisms were significantly associated with total body BMD in 1081 postmenopausal Japanese women. The rs12409277 SNP affected the transcriptional activity of PRDM16. The subjects with one or two minor allele(s) had a higher lean body mass than the subjects with two major alleles. Genetic analyses uncovered the importance of the PRDM16 gene in the regulation of lean body mass.
authors.affiliation: Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013851:Thinness / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C416371:PRDM16 protein, human; D014157:Transcription Factors
keywords: PRDM16; aging; body lean mass; genetics; genome-wide association study; single-nucleotide polymorphism