Alpha2-HS glycoprotein gene is associated with bone size at the hip in Chinese

Bone size is an important risk factor, independent of bone mineral density (BMD), for osteoporotic fracture. Bone size has a high heritability. A better understanding of genetic factors regulating bone size will have important clinical implications. In this study, we explored the relationship between the alpha2-HS glycoprotein (AHSG) gene and bone size variation at the spine and hip in a Chinese population. The study sample comprised 1 260 subjects from 401 Chinese nuclear families (each including both parents and at least one female child). The Sac / polymorphism inside the exon 7 of the AHSG gene was genotyped and analyzed. This variant represents a nucleotide substitution of C to G at amino acid position 238 resulting in a translation polymorphism of threonine to serine and thus making a potential impact on gene function. We assessed population stratification but did not find significant evidence at any skeletal sites. We found significant association between the AHSG Sac / polymorphism and bone size at the intertrochanteric region (P = 0.019) and the total hip (P = 0.035). The polymorphisms explained 3.74% and 3.16% variations in bone size at the intertrochanteric region and total hip respectively. No significant evidence of linkage was detected, largely due to the limited number of sibpairs in this data set and less informative marker (AHSG Sac / polymorphism) (compared with microsatellite markers) for linkage analysis. Our results suggested that the AHSG gene may contribute to bone size variation at the hip in this Chinese population.