GENETICS OF BONE DENSITY IN MEXICAN AMERICANS

描述：（改编自研究者摘要）骨质疏松症是一种 以骨质流失为特征的残疾状态。 有强有力 骨密度具有高度遗传性的证据，尽管相关基因 大部分都是未知的。 最近的研究表明维生素D受体， 尽管该基因在调节骨代谢中的重要性 争议 拟议研究的总体目标是确定和 表征低骨密度的遗传决定因素。 研究 人口将由750人组成，年龄在20岁及以上， 圣安东尼奥家庭心脏研究（SAFHS）的先前参与者。 期间 SAFHS的基线检查（1992-1996），广泛的访谈， 从所有个人获得广泛的医疗和生活方式 变量，包括饮食习惯和身体活动水平。 血液 并抽取样本及DNA作基因分析。 在 建议的研究，这些人将重新检查，骨密度将 通过双光子吸收测定法（DEXA）在三个部位测量。 额外 骨密度相关表型的生化标志物也将被 得到了 将对骨质疏松症的8个候选基因进行基因分型， 包括维生素D受体位点。 单独供资（作为 更新的SAFHS），资金已经提出了基因型a 一组跨越基因组的391个微卫星标记， 10 cM间隔。 将进行统计遗传分析，以确定 维生素D受体基因座，以及其他候选基因， 密度和相关性状。 将检测到主基因的证据 通过隔离分析。 这些基因将被映射到 使用微卫星标记的面板的染色体区域。 最后， 他们将测试基因对骨密度的影响是否会被 环境因素 例如，他们将确定钙摄入量是否 或体力活动与骨密度的相关性更强， 高风险维生素D受体基因型的个体比 在该位点具有较低风险基因型的个体。

DESCRIPTION: (Adapted from Investigator's Abstract) Osteoporosis is a disabling condition characterized by loss of bone mass. There is strong evidence that bone density is highly heritable, although the genes involved are largely unknown. Recent studies have implicated the vitamin D receptor, although the importance of this gene in modulating bone metabolism is controversial. The overall goal of the proposed study is to identify and characterize the genetic determinants of low bone density. The study population will consist of 750 individuals, aged 20 yrs and older, who are prior participants of the San Antonio Family Heart Study (SAFHS). During the baseline examination of the SAFHS (1992-1996), extensive interviews were obtained from all individuals on a wide range of medical and lifestyle variables, including dietary habits and physical activity levels. Blood samples were also drawn and DNA was collected for genetic analysis. In the proposed study, these individuals will be re-examined, and bone density will be measured at three sites by dual-photon absorptiometry (DEXA). Additional biochemical markers of bone density-related phenotypes will also be obtained. Eight candidate genes for osteoporosis will be genotyped, including the vitamin D receptor locus. Under separate funding (as part of the renewal for the SAFHS), funding has already been proposed to genotype a panel of 391 microsatellite markers spanning the genome at approximately 10cM intervals. Statistical genetic analyses will be performed to determine the effect of the vitamin D receptor locus, and of the other candidate genes, on bone density and related traits. Evidence for major genes will be detected through segregation analysis. These genes will then be mapped to chromosomal regions using the panel of microsatellite markers. Finally, they will test whether the genetic effects on bone density are modified by environmental factors. For example, they will determine if calcium intake or physical activity is more strongly correlated with bone density in individuals with the high risk vitamin D receptor genotype than in individuals with the lower risk genotypes at this locus.