Large‐scale analysis reveals a functional single‐nucleotide polymorphism in the 5′‐flanking region of PRDM16 gene associated with lean body mass

• Published in: Aging cell Vol. 13; no. 4; pp. 739 - 743
• Main Authors: Urano, Tomohiko, Shiraki, Masataka, Sasaki, Noriko, Ouchi, Yasuyoshi, Inoue, Satoshi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2014; BlackWell Publishing Ltd
• Subjects: 5' Flanking Region - genetics; aging; Alleles; Analysis; Animals; Body fat; body lean mass; Body mass; Body mass index; Body Weight - genetics; Bone density; Bone mineral density; Bones; Cell Line; Density; DNA-Binding Proteins - genetics; Female; Fractures; Gene polymorphism; Genes; Genetic analysis; Genetic aspects; Genetic Association Studies; Genetic factors; Genetic research; genetics; Genomes; genome‐wide association study; Human subjects; Humans; Lean body mass; Metabolism; Mice; Middle Aged; Musculoskeletal system; Original; Osteoporosis; Polymorphism; Polymorphism, Single Nucleotide - genetics; Post-menopause; Postmenopausal women; PRDM16; Sarcopenia; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Thinness - genetics; Transcription Factors - genetics; Transcription, Genetic; Type 2 diabetes; Womens health; genetics; aging; single-nucleotide polymorphism; PRDM16; genome-wide association study; body lean mass
• ISSN: 1474-9718; 1474-9726; 1474-9726
• DOI: 10.1111/acel.12228

Summary 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.