Zhang Z-L, He J-W, Qin Y-J, Hu Y-Q, Li M, Zhang H, Hu W-W, Liu Y-J, Gu J-M
The Department of Osteoporosis, Osteoporosis Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 600 Yi-Shan Rd, Shanghai, 200233, People's Republic of China.
Osteoporos Int. 2008 Jan;19(1):39-47. doi: 10.1007/s00198-007-0435-8. Epub 2007 Aug 17.
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.
Myostatin is a TGF-beta family member that is a negative regulator of skeletal muscle growth.
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.
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.
These results suggest, for the first time, the genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women.
我们通过测序在肌生成抑制素中鉴定出17个多态性位点，并选择了三个信息丰富的单核苷酸多态性（SNP）进行进一步观察，以研究它们与401个中国核心家庭中女性峰值骨密度的关联。我们的结果表明，肌生成抑制素中的基因多态性可能在中国女性峰值骨密度的获得中发挥作用。
肌生成抑制素是转化生长因子-β家族成员，是骨骼肌生长的负调节因子。
我们通过直接测序在肌生成抑制素中鉴定SNP。此外，使用定量传递不平衡检验（QTDT），我们测试并进一步检验SNP是否与401个中国核心家庭中脊柱和髋部的峰值骨密度（BMD）变化相关。我们通过测序在肌生成抑制素中鉴定出17个多态性位点。接下来，我们选择了三个信息丰富的SNP，进一步观察其与401个中国核心家庭中绝经前女性峰值骨密度的关联。
使用QTDT进行家系内关联分析时，我们发现rs2293284与全髋、股骨颈和大转子骨密度之间存在显著关联（所有p<0.05），而rs7570532与全髋和大转子骨密度相关（分别为p = 0.034和p = 0.035）。BMI与+2278G>A之间的家系内关联显著（p = 0.022）。随后的排列与这些显著的家系内关联结果一致。此外，单倍型分析为rs2293284和rs7570532与髋部峰值骨密度变化的关联提供了进一步证据。
这些结果首次表明，肌生成抑制素中的基因多态性可能在中国女性峰值骨密度的获得中发挥作用。
