Haplotype analysis of VDR gene polymorphisms: a meta-analysis
Haplotype analysis of VDR gene polymorphisms: a meta-analysis
复制标题
DOI：
10.1007/s00198-004-1601-x
复制
发表时间：
2004-09-01
影响因子：
4
通讯作者：
Attia, J
中科院分区：
文献类型：
--
作者：
Thakkinstian, A;D'Este, C;Attia, J
简介：虽然许多研究已经解决了维生素D受体（VDR）基因的多个个体多态性与骨骼健康之间的关系，但很少有人从单倍型的角度分析这些数据。我们对有关BsmI、ApaI和TaqI多态性数据的研究进行了荟萃分析，以（a）估计单倍型频率，（B）确定连锁不平衡（LD），（c）估计单倍型与骨质疏松症/骨矿物质密度（BMD）之间的关联程度。研究方法：单倍型使用期望最大化算法（EM）推断;对数线性模型用于确定与骨质疏松症的关联;方差分量回归分析用于确定与BMD的关联。结果如下：我们的研究结果表明，VDR基因最常见的单倍型，无论种族，是baT，其次是BAT和bAT在高加索人，和bAT和BaT在亚洲人。这表明BsmI和TaqI多态性之间的强LD。我们证明了当考虑单体型而不是单独的多态性时，功率的增加，即，尽管BsmI、ApaI和TaqI本身与骨质疏松症无显著相关性，但单倍型Bat和BAt与骨质疏松症显著相关，OR约为4。结论：我们已经将单倍型分析应用于VDR多态性和骨测量。我们还强调了一些方法学问题，包括连锁不平衡，EM算法在这种情况下的鲁棒性，以及探索效果修改的潜力。
Introduction: Although many studies have addressed the relationship between multiple individual polymorphisms in the vitamin D receptor (VDR) gene and bone health, few have analyzed this data in terms of haplotypes. We performed a meta-analysis of studies with data on the BsmI, ApaI, and TaqI polymorphisms in order to (a) estimate haplotype frequencies, (b) determine linkage disequilibrium (LD), and (c) estimate the magnitude of the association between haplotypes and osteoporosis/bone mineral density (BMD). Methods: Haplotypes were inferred using the expectation-maximization algorithm (EM); log-linear models were used to determine association with osteoporosis; and regression analysis with variance components was used to determine association with BMD. Results: Our results indicate that the most common haplotype for the VDR gene, regardless of ethnicity, is baT, followed by BAt and bAT in Caucasians, and bAT and BaT in Asians. This indicates strong LD between the BsmI and TaqI polymorphisms. We demonstrate a gain in power when considering the haplotypes rather than the individual polymorphisms separately, i.e., although BsmI, ApaI, and TaqI were not significantly associated with osteoporosis on their own, the haplotypes Bat and BAt were significantly associated, with an OR of approximately 4. Conclusion: We have applied haplotype analysis to the VDR polymorphisms and bone measures. We also highlight a number of methodologic issues, including linkage disequilibrium, the robustness of the EM algorithm in this context, and the potential for exploring effect modification.