Dennison E M, Arden N K, Keen R W, Syddall H, Day I N, Spector T D, Cooper C
MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
Paediatr Perinat Epidemiol. 2001 Jul;15(3):211-9. doi: 10.1046/j.1365-3016.2001.00350.x.
Studies of the association between polymorphisms of the gene for the vitamin D receptor (VDR) and adult bone mass have been inconsistent, pointing to the possibility that gene--environment interactions may vary in different populations. We have demonstrated previously an association between weight in infancy (a marker of the intrauterine and early post-natal environment) and each of adult bone mass and VDR genotype. We therefore sought to extend these observations in an elderly UK cohort and to investigate the possibility of an interaction between these genetic and early environmental markers of later osteoporosis risk. One hundred and sixty-five men and 126 women aged 61--73 years for whom birth records were available underwent bone mass measurements at baseline and follow-up 4 years later. Whole-blood samples were obtained, DNA extracted using standard techniques and polymorphisms in the VDR and collagen type I alpha 1 (Col IA1) genes identified. In the cohort as a whole, there were no significant associations between either birthweight or VDR genotype and bone mineral density (BMD) or bone loss rate at either site. However, the relationship between lumbar spine BMD and VDR genotype varied according to birthweight. Among individuals in the lowest third of birthweight, spine BMD was higher (P = 0.01) in individuals of genotype 'BB' after adjustment for age, sex and weight at baseline. In contrast, spine BMD was reduced (P = 0.04) in individuals of the same genotype who were in the highest third of the birthweight distribution. A significant (P = 0.02) statistical interaction was also found between VDR genotype and birthweight as determinants of BMD. Similar but slightly weaker associations were seen between lumbar spine bone mineral content (BMC) and VDR genotype in the lowest birthweight tertile. When examining the relationship between Col1A1 genotype and bone mass, lumbar spine BMC was higher in individuals of genotype 'Ss' or 'ss' in the lowest birthweight tertile (P = 0.02) after adjustment for age, sex and weight at baseline. These results suggest that genetic influences on adult bone size and mineral density may be modified by undernutrition in utero.
维生素D受体（VDR）基因多态性与成人骨量之间的关联研究结果并不一致，这表明基因 - 环境相互作用在不同人群中可能存在差异。我们之前已经证明婴儿期体重（子宫内和出生后早期环境的一个标志）与成人骨量及VDR基因型之间存在关联。因此，我们试图在一个英国老年队列中扩展这些观察结果，并研究这些遗传和早期环境标志物之间相互作用对后期骨质疏松症风险的影响。165名男性和126名年龄在61 - 73岁且有出生记录的女性在基线时进行了骨量测量，并在4年后进行了随访。采集全血样本，使用标准技术提取DNA，并鉴定VDR和I型胶原α1（Col IA1）基因的多态性。在整个队列中，出生体重或VDR基因型与任何一个部位的骨矿物质密度（BMD）或骨丢失率之间均无显著关联。然而，腰椎BMD与VDR基因型之间的关系因出生体重而异。在出生体重最低的三分之一人群中，经年龄、性别和基线体重校正后，“BB”基因型个体的脊柱BMD较高（P = 0.01）。相比之下，出生体重分布最高的三分之一人群中，相同基因型个体的脊柱BMD降低（P = 0.04）。还发现VDR基因型和出生体重作为BMD的决定因素之间存在显著的（P = 0.02）统计学相互作用。在出生体重最低的三分位数中，腰椎骨矿物质含量（BMC）与VDR基因型之间也观察到类似但稍弱的关联。在研究Col1A1基因型与骨量之间的关系时，经年龄、性别和基线体重校正后，出生体重最低三分位数中“Ss”或“ss”基因型个体的腰椎BMC较高（P = 0.02）。这些结果表明，子宫内营养不良可能会改变基因对成人骨骼大小和矿物质密度的影响。
