Heritability Estimations Of Bone Phenotypes And Relationship Between Estrogen Receptor Alpha Gene And Bone Phenotype And Body Mass Index

With the aging process and prevalence of global life-style, osteoporosis and obesity are becoming serious health problems. Bone mineral density (BMD) and bone size are independent risk factors for osteoporosis. High body mass index (BMI) is the standard diagnosis index of obesity. The present study has two aims. The first is to estimate the narrow-sense heritability of bone mineral density and bone size, and genetic correlations between bone phenotypes at different bone sites by full-sib pairs and mother-daughter pairs. The other is to test association and linkage between estrogen receptor alpha (ER-CC ) gene and bone mineral density, bone size and body mass index by quantitative transmission disequilibrium test (QTDT) program. All subjects were from 401 Chinese nuclear families (including father, mother and at least one daughter for each nuclear family). We measured the bone mineral density (g/cm2) and bone size (cm2) at the lumbar spine and hip using dual-energy X-ray absorptiometry (DXA) machine. Height (m) and weight (kg) were measured at the same time using standard medical instrument. Genotyping of the ER-alpha microsatellite polymorphism was performed using ABI 377 automated sequencer and affiliated software. When estimated by full-sib pairs and mother-daughter pairs, the narrow-sense heritabilities h1 (±SE) for bone mineral density at the spine were 0. 72(±0. 14) and 0. 44 (±0.07) , respectively, and for bone mineral density at the hip were 0.87 (±0. 14) and 0.77(±0.07), respectively.The significantly genetic correlation rG (±SE) of bone mineral density between the spine and hip were 0.97(±0.01) and 0. 76±(0. 04), respectively when estimated by full-sib pairs and mother-daughter pairs. When estimated by full-sib pairs and mother-daughter pairs, the narrow-sense heritabilities h2 (±520 for bone size at the spine were 0. 63(±0. 14) and 0.60 (±0. 07), respectively, and for bone size at the hip were 0. 45 (±0.14) and 0.69(±0.07), respectively. We did not find significantly genetic correlation between bone size at the spine and hip. These results indicate that both bone mineral density and bone size are under strong genetic control, and the variation of bone mineral density at the spine and hip may be affected by some common genetic factors. For the QTDT analyses in 384 nuclear families, significant association between bone mineral density and bone size and 5' polymorphisms of the ER-a gene was found, and the ER-a gene could account for minor variation of bone mineral density. For body mass index, we did not find, any significant association and linkage with the ER-a gene, which indicate the ER-a gene may not be a candidate gene associated with body mass index in Chinese.