Polymorphisms in the HOXD4 gene are not associated with peak bone mineral density in Chinese nuclear families

To determine the associations between HOXD4 gene polymorphisms with peak bone mineral density (BMD) throughing measuring three tagging single nucleotide polymorphisms (tagSNPs), including rs1867863, rs13418078, and rs4972504, in HOXD4. Four hundred Chinese nuclear families with male offspring (1215 subjects) and 401 Chinese nuclear families with female offspring (1260 subjects) were recruited. BMD of the lumbar spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. The quantitative transmission disequilibrium test (QTDT) was performed to investigate the association among the tagging SNPs, haplotypes and peak BMD. Only the CC genotype was identified in rs13418078 in the Chinese population, unlike other populations. We failed to find significant within-family association among these SNPs, haplotypes and peak BMD at any bone site in either male- or female-offspring nuclear families. The results suggest that genetic polymorphisms in HOXD4 may not be a major contributor to the observed variability in peak BMD in the lumbar spine and the hip in Chinese men and women.