title: Association between SNPs and haplotypes in the METTL21C gene and peak bone mineral density and body composition in Chinese male nuclear families.
abstract: The methyltransferase-like 21C gene (METTL21C), which is mainly expressed in muscle, can promote the differentiation of myoblasts to myotubes and reduce glucocorticoid-induced apoptosis of osteocytes. The purpose of this study was to explore the association between single nucleotide polymorphisms of METTL21C and peak bone mineral density (BMD), body mass index, total fat mass (TFM), and total lean mass (TLM) in Chinese young men. Fifteen tagging single nucleotide polymorphisms were genotyped, and haplotype blocks were derived in 400 Chinese male nuclear families. The peak BMD of the lumbar and hip, TFM, and TLM were measured by dual-energy X-ray absorptiometry. The association analyses were performed by a quantitative transmission disequilibrium test. Both TLM and TFM had a significant positive effect on peak BMD, but the positive regulation of TLM was stronger than that of TFM. After 1000 permutations, significant within-family associations were found between rs9585961 and lumbar spine BMD and femoral neck BMD, rs9518810 and femoral neck BMD, and rs599976 and body mass index, TFM, and percentage fat mass (all P < 0.05). The association analyses with haplotypes showed that haplotype AG in block 1 was significantly associated with TFM (P = 0.031) and haplotype CAG in block 2 was significantly associated with lumbar spine BMD (P = 0.020). Our study, for the first time, demonstrates that the polymorphisms and haplotypes of METTL21C contribute to the peak BMD and TFM in Chinese males, which suggests that as a quantitative trait locus with potential pleiotropy it may have an influence on osteoporosis and obesity.
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.|Department of Endocrinology, Shanxi Medical University Affiliated First Hospital, Taiyuan, 030001, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Gao
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Zhan-Ying
authors.initials: ZY
authors.lastname: Wei
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China.
authors.forename: Yun-Qiu
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Shanxi Medical University Affiliated First Hospital, Taiyuan, 030001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, 200233, China. ZZL2002@medmail.com.cn.
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D015502:Absorptiometry, Photon; D044466:Asian People / Q000235:genetics*; D001823:Body Composition / Q000235:genetics* / Q000502:physiology; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D008780:Methyltransferases
keywords: Fat mass; METTL21C; Peak bone mineral density; Quantitative transmission disequilibrium test; Single nucleotide polymorphism