Implementation of personalized medicine for fracture risk assessment in osteoporosis.
Implementation of personalized medicine for fracture risk assessment in osteoporosis.
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骨质疏松症骨折风险评估的个性化医疗的实施。
DOI：
10.1111/ggi.12721
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Mori S;Zhou H
本综述总结了我们在1995年至2011年间在东京都老年医院进行的连续日本尸检病例中识别与骨质疏松性骨折相关的遗传多态性并建立遗传风险评分（GRS）来预测骨折风险的努力。在转化生长因子β 1，rs 1800470;血小板反应蛋白，1型，含结构域7A，rs 12673692;和甲酰亚胺转移酶N-末端亚结构域含基因，rs7605378中的三个单核苷酸多态性显示与椎骨骨折患病率显著相关，而5个单核苷酸多态性与椎骨骨折患病率显著相关。（α-l-艾杜糖醛酸酶，rs3755955; C7 orf 58，rs 190543052;同源框C4，rs75256744;含G斑块结构域基因1，rs 2287679; Werner综合征，rs 2230009）与股骨骨折显著相关。GRS值计算为风险等位基因计数（未加权GRS）或从逻辑回归系数估计的加权评分（加权GRS）的总和。使用5个单核苷酸多态性的两个GRS值充分预测了924例男性受试者的股骨骨折患病率;受试者工作特征曲线下面积分别为0.750（95%置信区间[CI] 0.660-0.840）和0.770（95% CI 0.681-0.859）。Logistic回归分析显示，骨折患病率与未加权GRS ≥3（n= 124）和GRS < 3（n= 797）相关的比值比为8.39（95%CI 4.22- 16.69，P < 0.001）。加权GRS评分6-15分（n= 135）与GRS评分0-5分（n= 786）的比值比为7.73（95%CI 3.89- 15.36，P < 0.001）。因此，基于这五种单核苷酸多态性的风险等位基因谱的GRS可以帮助识别高危个体，并实施股骨骨折的预防措施。GeriatrGerontolInt 2016; 16（Suppl. 1）：57-65。
The present review summarizes our efforts to identify genetic polymorphisms associated with osteoporotic fractures and to establish a genetic risk score (GRS) to predict fracture risk in consecutive Japanese autopsy cases carried out at Tokyo Metropolitan Geriatric Hospital between 1995 and 2011. Three single nucleotide polymorphisms in transforming growth factor β‐1, rs1800470; thrombospondin, type 1, domain‐containing 7A, rs12673692; and formiminotransferase N‐terminal subdomain‐containing gene, rs7605378, showed a significant association with vertebral fracture prevalence, whereas five (α‐l‐iduronidase, rs3755955;C7orf58, rs190543052; homeobox C4, rs75256744; G patch domain‐containing gene 1, rs2287679; and Werner syndrome, rs2230009) were significantly associated with femoral fracture. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or of weighted scores estimated from logistic regression coefficients (weighted GRS). Both GRS values using the five single nucleotide polymorphisms adequately predicted femoral fracture prevalence for 924 male subjects; the areas under receiver‐operating characteristic curves were 0.750 (95% confidence interval [CI] 0.660–0.840) and 0.770 (95% CI 0.681–0.859), respectively. Logistic regression analysis showed that the odds ratio for the association between fracture prevalence and unweighted GRS ≥3 (n= 124) was 8.39 (95% CI 4.22–16.69,P< 0.001) relative to GRS < 3 (n= 797). Likewise, the odds ratio for a weighted GRS of 6–15 (n= 135) was 7.73 (95% CI 3.89–15.36,P< 0.001) relative to GRS 0–5 (n= 786). Therefore, the GRS based on the risk allele profiles of these five single nucleotide polymorphisms could help identify at‐risk individuals and enable implementation of preventive measures for femoral fracture.GeriatrGerontolInt 2016; 16 (Suppl. 1): 57–65.