Shaffer John R, Kammerer Candace M, Bruder Jan M, Cole Shelley A, Dyer Thomas D, Almasy Laura, Maccluer Jean W, Blangero John, Bauer Richard L, Mitchell Braxton D
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, 130 DeSoto Street, A300 Crabtree Hall, GSPH, Pittsburgh, PA 15213, USA.
Calcif Tissue Int. 2009 Feb;84(2):75-84. doi: 10.1007/s00223-008-9197-3. Epub 2008 Dec 9.
Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however, the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants in the San Antonio Family Osteoporosis Study. BMD change in 327 Mexican Americans (ages 25-45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h(2)) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm and to estimate heritability for BMD change of lumbar spine. BMD change was significantly heritable for total hip, ultradistal radius, and 33% radius (h(2) = 0.34, 0.34, and 0.27, respectively; p < 0.03 for all), modestly heritable for femoral neck (h(2) = 0.22; p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. In conclusion, we observed that change in BMD in young adults is heritable and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests that this region may harbor one or more genes involved in regulating early BMD change of the femoral neck.
骨质流失早在三十岁时就开始出现,其在整个成年期的累积效应可能会影响晚年患骨质疏松症的风险。然而,影响早期骨质流失的基因和环境因素在很大程度上尚不清楚。我们在圣安东尼奥家族骨质疏松症研究中调查了基因在骨矿物质密度(BMD)变化中的作用。从32个扩展家系的327名墨西哥裔美国人(年龄在25 - 45岁之间)的双能X线吸收法(DXA)测量值计算基线和随访(3.5至8.9年后)时的BMD变化。基于家系的似然方法用于估计遗传力(h(2)),并对股骨近端和前臂的BMD变化进行全常染色体连锁分析,以及估计腰椎BMD变化的遗传力。全髋关节、桡骨远极和33%桡骨处的BMD变化具有显著遗传性(h(2)分别为0.34、0.34和0.27;所有p值均<0.03),股骨颈处具有中等遗传性(h(2) = 0.22;p = 0.06),而脊柱BMD不具有遗传性。与BMD变化相关的协变量包括年龄、性别、基线BMD、绝经状态、体重指数以及期间的BMI变化,这些协变量解释了6%至24%的表型变异。在1号染色体1q23处观察到一个与股骨颈BMD变化相关的显著数量性状位点(LOD = 3.6)。总之,我们观察到年轻人的BMD变化具有遗传性,并进行了首批关于BMD变化的连锁研究之一。与1号染色体1q23的连锁表明该区域可能含有一个或多个参与调节股骨颈早期BMD变化的基因。