维生素D受体基因多态性在骨质疏松症和家族性骨质疏松症中的作用。

The contribution of vitamin D receptor gene polymorphisms in osteoporosis and familial osteoporosis.

作者信息

Fountas L, Moutsatsou P, Kastanias I, Tamouridis N, Tzanela M, Anapliotou M, Sekeris C E

机构信息

Department of Biological Chemistry, Medical School, National University of Athens, Greece.

出版信息

Osteoporos Int. 1999;10(5):392-8. doi: 10.1007/s001980050245.

DOI:10.1007/s001980050245

PMID:10591837

Abstract

It is well established that genetic factors play a major role in the pathogenesis of osteoporosis. Previous reports have suggested that vitamin D receptor (VDR) gene polymorphisms, particularly the BB, tt and AA genotypes, are associated with low bone mineral density (BMD). If these VDR genotypes are indeed an important determinant of BMD, then a population of related osteoporotic individuals (mother-daughter or sister-sister relationship) should have a high prevalence of the BB, tt or AA VDR genotypes. To test this hypothesis we determined the VDR genotypes in 26 osteoporotic persons (age 44.3 +/- 12.7 years, mean +/- SD) belonging to 12 families. Furthermore, for comparison with existing studies, we applied the VDR genotype analysis in a population of 53 unrelated healthy subjects (age 45.2 +/- 9.8 years, mean +/- SD) and 59 unrelated osteoporotic subjects (age 52.1 +/- 9.0 years, mean +/- SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly early postmenopausal. The proportions of the three genotypes, BB, tt and AA, within the 12 osteoporotic families were 15%, 12% and 27%, respectively, whereas the proportions of the other three homozygous genotypes (bb, TT, aa) were 50%, 50% and 23%. The distribution of the BB, tt and AA genotypes in the normal population was 21%, 21% and 36%, respectively (vs bb, TT, aa: 36%, 38%, 21%), whereas in the osteoporotic population it was 24%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data indicate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the population of unrelated normal or osteoporotic subjects. VDR genotype analysis showed no significant relation between VDR polymorphisms and BMD or Z-score values at the lumbar spine. This study demonstrates the lack of a heritability pattern between the BB, tt and AA genotypes and low BMD.

摘要

众所周知，遗传因素在骨质疏松症的发病机制中起主要作用。先前的报告表明，维生素D受体（VDR）基因多态性，尤其是BB、tt和AA基因型，与低骨密度（BMD）有关。如果这些VDR基因型确实是骨密度的重要决定因素，那么一群相关的骨质疏松个体（母女或姐妹关系）中BB、tt或AA VDR基因型的患病率应该很高。为了验证这一假设，我们测定了属于12个家庭的26名骨质疏松患者（年龄44.3±12.7岁，平均±标准差）的VDR基因型。此外，为了与现有研究进行比较，我们对53名无亲缘关系的健康受试者（年龄45.2±9.8岁，平均±标准差）和59名无亲缘关系的骨质疏松受试者（年龄52.1±9.0岁，平均±标准差）进行了VDR基因型分析。健康人群和骨质疏松人群的绝经状态为绝经前、围绝经期和大多为绝经后早期。在12个骨质疏松家庭中，BB、tt和AA这三种基因型的比例分别为15%、12%和27%，而其他三种纯合基因型（bb、TT、aa）的比例分别为50%、50%和23%。正常人群中BB、tt和AA基因型的分布分别为21%、21%和36%（vs bb、TT、aa：36%、38%、21%），而在骨质疏松人群中分别为24%、20%和34%（vs bb、TT、aa：27%、34%、14%）。我们的数据表明，与无亲缘关系的正常或骨质疏松受试者群体中的相同基因型相比，骨质疏松家庭中VDR基因型频率没有统计学上的显著差异（p>0.05）。VDR基因型分析显示VDR多态性与腰椎的骨密度或Z评分值之间没有显著关系。这项研究表明，BB、tt和AA基因型与低骨密度之间缺乏遗传模式。