The implication of assessing a polymorphism in estrogen receptor alpha gene in the risk assessment of osteoporosis using a screening tool for osteoporosis in Asians

Both genetic and environmental factors interact to determine bone mass and the risk for developing postmenopausal osteoporosis. Recently, an Asian-specific tool, the Osteoporosis Self-Assessment Tool for Asians (OSTA), has been developed to assess the risk of osteoporosis in women. An index is calculated by multiplying the difference in body weight in kilograms and age in years by 0.2 and disregarding the decimal digits. The risk of osteoporosis is classified as high, intermediate or low according to the OSTA index less than −4, −4 to −1 and greater than −1. In the present study we examined how a single nucleotide polymorphism (SNP) in exon 8 of the estrogen receptor α (ERα) gene affected the predictive value of the OSTA index. Subjects consisted of 358 postmenopausal women who were at least 55 years old. BMDs were measured by DXA, and the SNP in the ERα gene was assessed by PCR-RFLP. When considering both the OSTA index and ERα genotype in a logistic regression model, it was found that both the OSTA index and the ERα genotype independently contributed to the risk of osteoporosis. The odds ratios were 1.58 (95% CI 1.26–1.91) and 2.51 (95% CI 1.42–4.44) for one unit decrement in the OSTA index and each copy of the A allele of the ERα genotype, respectively. The joint effect conformed more to a multiplicative model of interaction than an additive model. This suggests that persons with the high-risk genotype are at far greater risk of developing osteoporosis with advancing age or decreasing body weight, the two variables from which the OSTA index is derived. Targeting preventive measures for osteoporosis subjects with risk factors and also disease-susceptibility alleles is likely to be more cost effective.