Dataset Information

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 +2278GA 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.

SUBMITTER: Yue H

PROVIDER: S-EPMC4010361 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

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

Yue Hua H He Jin-wei JW Zhang Hao H Wang Chun C Hu Wei-wei WW Gu Jie-mei JM Ke Yao-hua YH Fu Wen-zhen WZ Hu Yun-qiu YQ Li Miao M Liu Yu-juan YJ Wu Song-hua SH Zhang Zhen-lin ZL

Acta pharmacologica Sinica 20120319 5

<h4>Aim</h4>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.<h4>Methods</h4>Four hundred male-offspring nuclear families of Chinese Han ...[more]

PMID: 22426697

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Project description:IntroductionFew studies have deciphered whether lean body mass (LBM) or fat mass (FM) is predominantly responsible for the body mass index (BMI)-hypertension association. This study aimed to assess the associations of predicted LBM and FM with hypertension risk among Chinese male adults.MethodsA prospective cohort study was conducted among 2,812 male participants free of hypertension in the Fangchenggang Area Males Health and Examination Survey in 2009. We performed multivariable Cox models and restricted cubic spline to examine the associations of predicted LBM and FM and BMI with hypertension, and to further explore the mediating roles of lipid and glycemic traits in the relationship between predicted FM and blood pressure.ResultsOf 1,238 participants included in the cohort study, 306 (24.8%) hypertension cases were identified during a median follow-up of 3.8 years, with an incidence rate of 7.0 per 100 person-years. A positive linear-shaped association was consistently observed between BMI and hypertension (p for trend <0.001). Multivariable-adjusted Cox models including predicted LBM and FM observed a positive association between predicted FM and hypertension. Compared with those in the lowest quartile of predicted FM, men in the highest quartile had a hazard ratio (HR) of 1.83 (95% confidence interval (CI): 1.13-2.97) for hypertension. The HR per standard deviation increase of BMI and predicted FM was 1.11 (95% CI: 1.04-1.19) above 23.1 kg/m2 and 1.05 (95% CI: 1.02-1.15) above 14.6 kg, respectively. However, predicted LBM was not associated with hypertension. In addition, high-density lipoprotein cholesterol (HDL-c) and fasting blood glucose (FBG) mediated the relationship of predicted FM with systolic blood pressure, with a mediation ratio of 37.1% and 8.2%, respectively. Furthermore, total cholesterol (TC) and triglyceride (TG) positively mediated the association of predicted FM with diastolic blood pressure, with a mediation ratio of 9.5% and 9.9%, respectively.ConclusionHigher predicted FM might play a central role in the positive linear relationship of the BMI-hypertension association in Chinese male adults, and the link from predicted FM to blood pressure was partially mediated by TC, TG, HDL-c, and FBG.

Project description:BackgroundGeneralised high bone mass (HBM), associated with features of a mild skeletal dysplasia, has a prevalence of 0.18% in a UK DXA-scanned adult population. We hypothesized that the genetic component of extreme HBM includes contributions from common variants of small effect and rarer variants of large effect, both enriched in an extreme phenotype cohort.MethodsWe performed a genome-wide association study (GWAS) of adults with either extreme high or low BMD. Adults included individuals with unexplained extreme HBM (n = 240) from the UK with BMD Z-scores ≥+3.2, high BMD females from the Anglo-Australasian Osteoporosis Genetics Consortium (AOGC) (n = 1055) with Z-scores +1.5 to +4.0 and low BMD females also part of AOGC (n = 900), with Z-scores -1.5 to -4.0. Following imputation, we tested association between 6,379,332 SNPs and total hip and lumbar spine BMD Z-scores. For potential target genes, we assessed expression in human osteoblasts and murine osteocytes.ResultsWe observed significant enrichment for associations with established BMD-associated loci, particularly those known to regulate endochondral ossification and Wnt signalling, suggesting that part of the genetic contribution to unexplained HBM is polygenic. Further, we identified associations exceeding genome-wide significance between BMD and four loci: two established BMD-associated loci (5q14.3 containing MEF2C and 1p36.12 containing WNT4) and two novel loci: 5p13.3 containing NPR3 (rs9292469; minor allele frequency [MAF] = 0.33%) associated with lumbar spine BMD and 11p15.2 containing SPON1 (rs2697825; MAF = 0.17%) associated with total hip BMD. Mouse models with mutations in either Npr3 or Spon1 have been reported, both have altered skeletal phenotypes, providing in vivo validation that these genes are physiologically important in bone. NRP3 regulates endochondral ossification and skeletal growth, whilst SPON1 modulates TGF-β regulated BMP-driven osteoblast differentiation. Rs9292469 (downstream of NPR3) also showed some evidence for association with forearm BMD in the independent GEFOS sample (n = 32,965). We found Spon1 was highly expressed in murine osteocytes from the tibiae, femora, humeri and calvaria, whereas Npr3 expression was more variable.ConclusionWe report the most extreme-truncate GWAS of BMD performed to date. Our findings, suggest potentially new anabolic bone regulatory pathways that warrant further study.

Project description:BackgroundLittle is known about the association of changes in two body components, muscle and fat mass, with the risk of cardiovascular disease (CVD) among young adults. We investigated the association of changes in predicted lean body mass index (LBMI), appendicular skeletal muscle mass index (ASMI), and body fat mass index (BFMI) with the development of CVD among young adults.MethodsThis nationwide, population-based cohort study included 3 727 738 young adults [2 406 046 (64.5%) men and 1 321 692 (35.5%) women] aged 20-39 years without a previous history of CVD who underwent two health screening examinations during 2009-2010 and 2011-2012. Using validated and robust prediction equations, we calculated the changes in predicted LBMI, ASMI, and BFMI from the first to the second examinations.ResultsThe mean (SD) age was 32.2 (4.9) years, and 2 406 046 (64.5%) of the participants were men. A total of 23 344 CVD events were detected during 22 257 632 person-years of follow-up. Each 1 kg/m2 increase in predicted LBMI and ASMI change was associated with a reduced risk of CVD among men [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI) 0.82-0.91; aHR: 0.76, 95% CI 0.69-0.82, respectively] and women (aHR: 0.77, 95% CI 0.63-0.95; aHR: 0.75, 95% CI 0.59-0.96). Each 1 kg/m2 increase in predicted BFMI change was associated with an increased risk of CVD among men (aHR: 1.16, 95% CI 1.10-1.22) and women (aHR: 1.32, 95% CI 1.06-1.65). In both sexes, decreases in predicted LBMI and ASMI were associated with greater CVD risk, and decreased predicted BFMI was associated with a reduced CVD risk. Those who maintained their BMI between -1 and +1 kg/m2 also had a decreased risk of CVD per 1 kg/m2 increase in predicted LBMI and ASMI change among men (aHR: 0.86, 95% CI 0.80-0.92; aHR: 0.85, 95% CI 0.76-0.95) and women (aHR: 0.62, 95% CI 0.47-0.83; aHR: 0.59, 95% CI 0.44-0.80) and had a greater risk of CVD per 1 kg/m2 increase in predicted BFMI change among men (aHR: 1.17, 95% CI 1.10-1.25) and women (aHR: 1.64, 95% CI 1.20-2.23). Regardless of changes in weight, such as from normal to obese or vice versa, these results were consistent.ConclusionsAmong young adults, increased predicted muscle mass or decreased predicted fat mass were associated with a reduced risk of development of CVD. Decreased predicted muscle mass or increased predicted fat mass were associated with an elevated risk of development of CVD.

Project description:BackgroundStudies on the prospective association of body composition with mortality in US general populations are limited. We aimed to examine this association by utilizing data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with data from the National Death Index.MethodsWe analysed data of NHANES 1988-1994 and 1999-2014, with 55 818 participants [50.6% female, baseline mean age: 45.0 years (SE, 0.2)]. Predicted fat mass and lean mass were calculated using the validated sex-specific anthropometric prediction equations developed by the NHANES based on individual age, race, height, weight, and waist circumference. Body composition and other covariates were measured at only one time point. Multivariable Cox regression was used to investigate the associations of predicted fat mass and lean mass with overall and cause-specific mortality, adjusting for potential confounders. Interactions between age and body composition on mortality were examined with likelihood ratio testing.ResultsMean predicted fat mass was 24.1 kg [95% confidence interval (CI): 23.9-24.3) for male participants and 29.9 kg (95% CI: 29.6-30.1) for female participants, while mean predicted lean mass was 59.3 kg (95% CI: 59.1-59.5) for male participants and 41.7 kg (95% CI: 41.5-41.8) for female participants. During a median period of 9.7 years from the survey, 10 408 deaths occurred. When predicted fat and lean mass were both included in the model, predicted fat mass showed a U-shaped association with all-cause mortality, with significantly higher risk at two ends: Quintile 1 (HR, 1.17; 95% CI: 1.05-1.31), Quintile 2 (HR, 1.14; 95% CI: 1.04-1.26) and Quintile 5 (HR, 1.37; 95% CI: 1.12-1.68) compared with Quintile 3. In contrast, predicted lean mass showed a L-shaped association with all-cause mortality, with higher mortality in those with lower lean mass: Quintile 1 (HR, 1.64; 95% CI: 1.46-1.83) and Quintile 2 (HR, 1.29; 95% CI: 1.18-1.42) compared with Quintile 3. Similar results were found for cardiovascular, cancer, and respiratory cause-specific mortality. Age was a significant modifier: There was a monotonic positive association of predicted fat mass with mortality in younger participants (<60 years), but an approximate J-shaped association in older participants (≥60 years) (P interaction <0.001); there was a stronger inverse association between predicted lean mass and mortality in older participants (≥60) compared with those <60 years (P interaction <0.001).ConclusionsIn this US general population, predicted fat mass and lean mass were independent predictors for overall and cause-specific mortality. Age was a significant modifier on the associations.

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Dataset Information

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

Aim

Methods

Results

Conclusion

Publications

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

Similar Datasets

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