Contribution of Myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring

Abstract

Aim: Myostatin gene is a member of the transforming growth factor-β (TGF-β) family that negatively regulates skeletal muscle growth. Genetic polymorphisms in Myostatin were found to be associated with the peak bone mineral density (BMD) in Chinese women. The purpose of this study was to investigate whether Myostatin played a role in the normal variation in peak BMD, lean mass (LM), and fat mass (FM) of Chinese men. Methods: Four hundred male-offspring nuclear families of Chinese Han ethnic group were recruited. Anthropometric measurements, including the peak BMD, body LM and FM were measured using dual-energy X-ray absorptiometry (DXA). The single nucleotide polymorphisms (SNPs) studied were tag-SNPs selected by sequencing. Both rs2293284 and +2278G﹥A were genotyped using TaqMan assay, and rs3791783 was genotyped with PCR-restriction fragment length polymorphism (RFLP) analysis. The associations of the SNPs with anthropometric variations were analyzed using the quantitative transmission disequilibrium test (QTDT). Results: Using QTDT to detect within-family associations, neither single SNP nor haplotype was found to be associated with peak BMD at any bone site. However, rs3791783 was found to be significantly associated with fat mass of the trunk (P<0.001). Moreover, for within-family associations, haplotypes AGG, AAA, and TGG were found to be significantly associated with the trunk fat mass (all P<0.001). Conclusion: Our results suggest that genetic variation within Myostatin may play a role in regulating the variation in fat mass in Chinese males. Additionally, the Myostatin gene may be a candidate that determines body fat mass in Chinese men.

Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development

“…Although the role of myostatin in muscle growth regulation has been widely investigated, its role in regulating bone mass, architecture and regeneration is becoming an area of increased interest. Genetic studies in human populations have shown that myostatin gene polymorphisms are associated with variation in peak bone mineral density [140], and transgenic overexpression of myostatin propeptide, which inhibits myostatin signaling in vivo, increases BMD in mice [141]. Thus, there is evidence from both human studies and animal models to suggest that myostatin is an important regulator of both muscle mass and bone density.…”

Joint dysfunction and functional decline in middle age myostatin null mice

“…Myostatin also inhibits expression of BMP2 and IGF1, decreases osteoblast differentiation, and reduces mineral formation in bone marrow-derived mesenchymal stem cells (43, 44). Furthermore, myostatin gene polymorphism is associated with variation in peak bone mineral density in humans (45, 46). These data together indicate that prolonged myostatin blockade may reduce the endogenous restraint on pro-osteogenic tissue remodeling, resulting in bone and soft tissue alterations and impaired the ankle joint function with aging.…”

BMP7 gene polymorphisms are not associated with bone mineral density or osteoporotic fractures in postmenopausal Chinese women

“…Quality assurance scans were conducted by scanning an aluminum spine phantom according to the manufacturer's instructions. The coefficient of variability (CV) values of the DXA measurements of the lumbar spine, femoral neck, and total hip were 1.39%, 2.22%, and 0.70%, respectively [15][16][17] . All DXA scans were conducted by the same welltrained technologist throughout the study.…”