Malkin Ida, Ermakov Sergey, Kobyliansky Eugene, Livshits Gregory
Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Hum Genet. 2006 Aug;120(1):42-51. doi: 10.1007/s00439-006-0173-6. Epub 2006 Apr 26.
Loss of bone strength is the main determinant of bone fragility. Bone strength is directly dependent on bone size (BS). A substantial portion of BS variation is attributable to genetic effects. However, the list of genes and allelic variants involved in the determination of BS variation is far from being complete. Polymorphisms in the ANKH gene have been shown to be associated with radiographic hand BS-related phenotypes. The present study examined the possible association of the ANKH gene with skeletal size and shape in order to test the universality of the ANKH effect on BS traits. Our sample consisted of a total of 212 ethnically homogeneous nuclear families (743 individuals) of European origin. Each individual was measured for body height, weight, and several other anthropometrical measurements, and genotyped for nine polymorphic markers (the average heterozygosity level was 0.4). We observed significant associations with practically all the anthropometrical phenotypes studied. More specifically, we found associations with body weight and height, limb length (P</=0.001; promoter region). After adjustment for body height, we demonstrated the substantial association increase for biacromial breadth (P=0.0012; some 140 kb downstream from ANKH) and vertebral column length (P=0.0008; exons 2-7 region). The majority of the observed associations persisted even after correction for multiple testing. For the first time the reliable evidence in support of universality of ANKH gene polymorphisms effect on bone size was provided.
骨强度丧失是骨脆性的主要决定因素。骨强度直接取决于骨大小（BS）。BS变异的很大一部分归因于遗传效应。然而，参与决定BS变异的基因和等位基因变异列表远未完整。ANKH基因多态性已被证明与手部X线片上与BS相关的表型有关。本研究检测了ANKH基因与骨骼大小和形状之间可能存在的关联，以检验ANKH对BS性状影响的普遍性。我们的样本包括总共212个欧洲裔的种族同质核心家庭（743人）。对每个个体测量身高、体重和其他一些人体测量指标，并对9个多态性标记进行基因分型（平均杂合度水平为0.4）。我们观察到与几乎所有研究的人体测量表型都存在显著关联。更具体地说，我们发现与体重、身高、肢体长度有关联（P≤0.001；启动子区域）。在对身高进行校正后，我们证明了肩峰间宽度（P = 0.0012；ANKH下游约140 kb处）和脊柱长度（P = 0.0008；外显子2 - 7区域）的关联显著增加。即使在进行多重检验校正后，大多数观察到的关联仍然存在。首次提供了可靠证据支持ANKH基因多态性对骨大小影响的普遍性。
