An IGF1 Promoter Polymorphism is Associated with Muscle Function in the Health ABC and FMS cohorts

Abstract

Changes in human body composition (BC) that occur with aging are typically detrimental to health. These changes contribute to a loss of physical function, osteoporosis, cardiovascular disease, and other diseases including diabetes. Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of BC. PURPOSE: To idenfity assocations of IGF1 with BC. METHODS: In the current study, participants from the Health, Aging, and Body Composition Study, white males and females (n=925/836) and black males and females (533/705) aged 70-79 years were genotyped for a polymorphism in the promoter region of the IGF1 gene (rs7965399, -T1245C). Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. An association with BC was identified in females when significant covariates (physical activity, age, smoking status, BMI) were included in the regression model. RESULTS: White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (p < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (p < 0.05). To validate and compare these findings, a cohort (the Functional SNPs Associated with Muscle Size and Strength; FMS) of young (mean age = 24.6, SD = 5.9) white men and women (n=173/296) with similar phenotypic measurements were genotyped. Associations were identified with muscle strength in women (p < 0.01) that were in agreement with the C/C genotype having lower muscle function. CONCLUSION: All associations were consistent with function of IGF1 being reduced in the C/C genotype. Thus, in an elderly population a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in females. Additionally, this association may be evident even in younger adults, providing more predictive power.