Association of the Myostatin Gene with Obesity, Abdominal Obesity and Low Lean Body Mass and in Non-Diabetic Asian Indians in North India



English: Excess adipose tissue around a male's...


Asian Indians are predisposed to develop the metabolic syndrome and type 2 diabetes (T2DM). Among other factors, a major factor contributing to metabolic risk is abnormal body composition. Asian Indians tend to have more abdominal adipose tissue, less lean body mass (LBM) and higher magnitude of insulin resistance (IR) despite falling in the normal range of body mass index (BMI) [1]. The high value of waist hip ratio in Asian Indians may be due to less lean mass of the hips and greater fat at the levels of waist [2]. Another study showed that Asian Indian men have low muscle mass and 30% more total body fat (BF) than other ethnic groups [3]. Low lean mass is also evident in Asian Indian neonates as compared to white Caucasian neonates [4]. Whether low muscle mass in Asian Indians is related to high IR and metabolic syndrome is not yet been adequately investigated. Finally, the reason for these characteristics of body composition has been often stated as due to the “genetic predisposition”, “ethnic factors”, and “chronic protein deprivation” but remains largely uninvestigated [5].


Muscle is the major target for insulin-stimulated glucose uptake, the key determinant of total body insulin sensitivity. Skeletal muscle is the major constituent of LBM and the major determinant of energy expenditure both at rest and during physical activity [6]. Skeletal muscle IR, due to decreased muscle glycogen synthesis, promotes atherogenic dyslipidemia by diverting energy derived from ingested carbohydrates away from muscle glycogen synthesis into increased hepatic de novolipogenesis. These findings are important for understanding the mechanism by which skeletal muscle IR promotes the development of the IR, the metabolic syndrome and T2DM [7].


Myostatin [growth/differentiation factor-8 (GDF-8)], belongs to the transforming growth factor β super family of secreted proteins that control growth and differentiation [8]. Myostatin is expressed uniquely in human skeletal muscle as a 26 kDa mature glycoprotein and secreted into the plasma [8][9]. Since the first report of human Myostatin gene in 1998 [9], six polymorphisms and one intronic mutation have been identified in the Myostatin gene [9][10][11].


A few studies are available regarding Myostatin gene and its functions in animals and humans. Zhiliang et al [12] reported that Myostatin gene in chickens not only plays an important role in controlling skeletal muscle growth and differentiation, but also appears to have some regulatory function on adipose tissue. In transgenic animal models, a lack of myostatin appears to reduce age-related sarcopenia and loss of muscle regenerative capacity [13]. In human studies, Ferrel et al. [14]studied A55T and K153R allelic variants in 49 Caucasians or African Americans, but did not find any significant impact of these polymorphisms in either races, however, a small effect could not be excluded. A loss-of-function mutation (G378A) in the Myostatin gene has been associated with muscle hypertrophy in the humans [15]. Gonzalez et al [16] studied 41 nonagenarians (33 women, age range, 90, 97 yrs) for A55T, E164K, I225T, K153R and P198A variants of Myostatin gene. According to these authors heterozygosity for the K153R polymorphism did not seem to exert any negative influence on the muscle phenotypes of women but homozygosity may do so. Further, Myostatin K153R polymorphism was investigated in 281 non-athletic young adults, where it was shown to be associated with the ability to produce ‘peak’ power during muscle contractions [17]. Overall, the genetic basis of muscle mass, and specifically the Myostatin gene, has been sparsely investigated in human beings.


We hypothesized that the A55T and K153R polymorphisms in the Myostatin gene may have an association with obesity, abdominal and truncal adiposity and LBM in non-diabetic Asian Indians. In this study, we assessed the polymorphic status of the Myostatin gene and its correlation with the measures of generalized and abdominal obesity and LBM in Asian Indians residing in north India.










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