Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the women's health and aging study II cohort

OBJECTIVES: To determine whether polymorphic variation in the myostatin gene differentially influences the maintenance of muscle strength in older adults, and to find supportive evidence in a cohort of older women. DESIGN: Correlation study of polymorphic variation in a cohort of older women. SETTING: Representatively sampled older female population living in the eastern half of Baltimore, Maryland. PARTICIPANTS: Participants were 286 women, age 70 to 79. Of these, 81.1% were Caucasian, 18.8% were African American, and 0.2% were Asian or Hispanic. MEASUREMENTS: Overall strength was measured with a dynamometer and defined as the sum of the strongest measures of hip, knee, and grip strength on the dominant side. RESULTS: We identified or confirmed six myostatin polymorphic variants in the Women's Health and Aging Study II population. Of the polymorphisms, K153R is the most common, with an allele frequency of 0.19 in African Americans. Unadjusted mean strength by genotype suggested lower muscle strength in those African-American women with the R genotype compared with those with the K genotype (K/K: 72.50 ± 13.9 kg (n = 39) vs K/R: 67.14 ± 11.4 kg (n = 13) vs R/R: 63.1 ± 11.3 kg (n = 3)). After adjustment for race in a linear regression model, the R genotype remained associated with lower strength levels (P = .04). Statistical significance decreased when body mass index and race were both added to the model (P = .09). CONCLUSIONS: Recognizing that small sample size in the study of genes of modest effect are unlikely to yield significant differences, these data suggest an association of the R153 allele with lower strength in high-functioning older women, which should be studied further in a larger cohort.