Miljkovic-Gacic Iva, Wang Xiaojing, Kammerer Candace M, Gordon Christopher L, Bunker Clareann H, Kuller Lewis H, Patrick Alan L, Wheeler Victor W, Evans Rhobert W, Zmuda Joseph M
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Obesity (Silver Spring). 2008 Aug;16(8):1854-60. doi: 10.1038/oby.2008.280. Epub 2008 May 29.
Increased fat infiltration in skeletal muscle has been associated with diabetes. Quantitative computed tomography (QCT) can be used to measure muscle density, which reflects the lipid content of skeletal muscle such that greater fat infiltration in skeletal muscle is associated with lower muscle density. The relative contribution of genetic and environmental factors to fat infiltration in skeletal muscle has not been assessed. Therefore, our aim is to determine genetic and environmental contributions to measures of skeletal muscle composition, and describe their associations with type 2 diabetes in multigenerational families of African ancestry.
Peripheral QCT (pQCT) measures of skeletal muscle density were obtained for the calf in 471 individuals (60% women; mean 43 years) belonging to eight large, multigenerational Afro-Caribbean families (mean family size 51 individuals; 3,535 relative pairs).
The proportion of variance in muscle density due to additive genetic effects (residual heritability) was 35.0% (P < 0.001) and significant covariates (age, gender, BMI, and parity) explained 55.0% of the total phenotypic variation in muscle density. Muscle density was lower (P < 0.001) in 62 diabetics (69.5 mg/cm(3)) than in 339 nondiabetics (74.3 mg/cm(3)) and remained significant after adjusting for age, gender, and BMI (P = 0.005) or age, gender, and waist circumference (P = 0.01).
Our results provide new evidence that ectopic lipid deposition in skeletal muscle is a heritable trait and is associated with diabetes, independent of overall and central obesity in families of African heritage. Genome-wide screens and candidate gene studies are warranted to identify the genetic factors contributing to ectopic deposition of skeletal muscle fat.
骨骼肌中脂肪浸润增加与糖尿病有关。定量计算机断层扫描（QCT）可用于测量肌肉密度，其反映骨骼肌的脂质含量，因此骨骼肌中脂肪浸润增加与较低的肌肉密度相关。尚未评估遗传和环境因素对骨骼肌脂肪浸润的相对贡献。因此，我们的目的是确定遗传和环境因素对骨骼肌组成测量的贡献，并描述它们在非洲裔多代家庭中与2型糖尿病的关联。
对属于八个大型多代非洲裔加勒比家庭（平均家庭规模51人；3535个亲属对）的471名个体（60%为女性；平均年龄43岁）的小腿进行外周QCT（pQCT）测量骨骼肌密度。
加性遗传效应（剩余遗传力）导致的肌肉密度方差比例为35.0%（P<0.001），显著协变量（年龄、性别、BMI和胎次）解释了肌肉密度总表型变异的55.0%。62名糖尿病患者的肌肉密度（69.5mg/cm³）低于339名非糖尿病患者（74.3mg/cm³）（P<0.001），在调整年龄、性别和BMI（P=0.005）或年龄、性别和腰围（P=0.01）后仍具有显著性。
我们的结果提供了新的证据，表明骨骼肌中的异位脂质沉积是一种可遗传的性状，并且与糖尿病相关，独立于非洲裔家庭中的总体和中心性肥胖。有必要进行全基因组筛查和候选基因研究，以确定导致骨骼肌脂肪异位沉积的遗传因素。
