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.
Highlights
Loss of skeletal muscle mass and function is a common disorder in the elderly (Karakelides & Nair, 2005; Cruz-Jentoft et al, 2010)
A number of large-scale genome-wide association (GWA) studies have found novel single-nucleotide polymorphisms (SNPs) associated with complex diseases or traits, including bone mineral density (BMD), fat content, and body mass index (Hirschhorn & Daly, 2005; Wang et al, 2010)
We used the Affymetrix 250K SNP GeneChip (262 000 SNPs) to examine the genetic association of SNPs with lean body mass adjusting with age in 269 subjects
Summary
Loss of skeletal muscle mass and function is a common disorder in the elderly (Karakelides & Nair, 2005; Cruz-Jentoft et al, 2010). Sarcopenia is a common skeletal muscle disease characterized by low lean body mass of muscle tissue, leading to decreased skeletal strength and increased susceptibility to fracture. The identification of novel candidate genes that contribute to low lean body mass susceptibility will impact the diagnosis and treatment for disorders such as sarcopenia. A large-scale association study is an unbiased approach that involves scanning the entire human genome to identify novel genes or genomic regions with modest effects on complex human diseases and traits. A number of large-scale GWA studies have found novel single-nucleotide polymorphisms (SNPs) associated with complex diseases or traits, including bone mineral density (BMD), fat content, and body mass index (Hirschhorn & Daly, 2005; Wang et al, 2010)
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