Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families

Summary: We identified 17 polymorphisms in myostatin by sequencing, and three informative single nucleotide polymorphisms (SNPs) were selected for further observation for their association with peak BMD of women in 401 Chinese nuclear families. Our results suggest that genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women. Introduction: Myostatin is a TGF-beta family member that is a negative regulator of skeletal muscle growth. Materials and methods: We identified SNPs in myostatin by direct sequencing. Furthermore, using a quantitative transmission disequilibrium test (QTDT). we tested and further test whether SNPs were associated with peak bone mineral density (BMD) variation at the spines and hips of 401 Chinese nuclear families. We identified 17 polymorphisms in myostatin by sequencing. Next, we selected three informative SNPs for further observation of an association with peak BMD of premenopausal women in 401 Chinese nuclear families. Results: Using QTDT for the within-family association, we found significant association between rs2293284 and total hip, femoral neck, and trochanter BMD (all p<0.05), while rs7570532 was associated with total hip and trochanter BMD (p=0.034 and p=0.035, respectively). The within-family association was significant between BMI and +2278G>A (p=0.022). Subsequent permutations were in agreement with these significant within-family association results. Moreover, analyses of the haplotypes confer further evidence for association of rs2293284 and rs7570532 with hip peak BMD variation. Conclusions: These results suggest, for the first time, the genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women.