Contribution of the sclerostin domain-containing protein 1 (SOSTDC1) gene to normal variation of peak bone mineral density in Chinese women and men

A genome-wide linkage analysis in Chinese families revealed a significant quantitative trait loci on chromosome 7p21.1 for femoral neck bone mineral density (BMD) (LOD = 3.68), and a potential candidate gene, sclerostin domain-containing protein 1 (SOSTDC1), is located in this region. SOSTDC1 belongs to a class of bone morphogenetic protein (BMP) antagonists that bind BMPs and regulate their signaling. We therefore genotyped 6 tag single nucleotide polymorphisms (tag-SNPs) in SOSTDC1 gene using allele-specific PCR method and investigated the association between SOSTDC1 gene polymorphisms and peak BMD variation in 401 Chinese female-offspring nuclear families (including 1260 subjects) and 400 Chinese male-offspring nuclear families (including 1215 subjects), respectively. Using both family-based (quantitative transmission disequilibrium test) and population-based (ANOVA) methods of analyses, BMD values were adjusted for age, height and weight. In female-offspring nuclear families, we found a significant within family association between rs16878759 and the lumbar spine peak BMD (P = 0.003) and rs16878759 accounted for 1.4% of the lumbar spine peak BMD variation. Moreover, haplotype CCC (containing rs12699800, rs16878759, and rs17619769) had a significant within family association with the lumbar spine peak BMD (P = 0.001) and accounted for 1.9% of the peak BMD variation at this bone site. However, in the male-offspring nuclear families, we failed to detect any significant association between any SNP or haplotype and peak BMD at any bone site. In conclusion, our results indicate for the first time that the genetic polymorphisms in SOSTDC1 have an effect on attainment and maintenance of peak bone mass in Chinese women.