Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects
Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects
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DOI：
10.1007/s00439-010-0881-9
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发表时间：
2010-11-01
期刊：
影响因子：
5.3
通讯作者：
Zhao, Lan-Juan
中科院分区：
文献类型：
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作者：
Bu, Feng-Xiao;Armas, Laura;Zhao, Lan-Juan
维生素 D 缺乏症是美国常见的公共卫生问题。与佝偻病、骨质疏松等疾病的高发风险有关。目前，血清25-羟基维生素D [25(OH)D]浓度是维生素D状态以及确定其缺乏或充足的最佳指标。该水平具有较高的遗传力（28-80%）。然而，导致血清 25(OH)D 广泛变异的基因通常未知。在这项研究中，我们使用 49 个单核苷酸多态性 (SNP) 标记在 156 名不相关的健康白人受试者中筛选了维生素 D 代谢途径中的 9 个重要基因。可能影响血清 25(OH)D 变异的显着混杂因素被用作关联分析的协变量。进行数量性状的关联检验以评估候选基因与血清25(OH)D水平之间的关联。进行排列是为了纠正多个测试问题。在 CYP2R1（细胞色素 P450，家族 2，亚家族 R，多肽 1）和 GC（维生素 D 结合蛋白）基因中的 SNP 处观察到关联证据。接下来，我们使用另一组 340 名不相关的健康白人受试者，对基因 CYP2R1 和 GC 中的 6 个有前景的 SNP 进行了复制研究。在复制队列 (n = 340) 和合并队列 (n = 496) 中进行关联分析。 CYP2R1 基因和 GC 基因在合并队列中仍然很重要。结果表明，CYP2R1 和 GC 基因可能导致健康人群血清 25(OH)D 水平的变化。
Vitamin D deficiency is a common public health problem in the US. It is related to the high risk of rickets, osteoporosis and other diseases. Currently, serum 25-hydroxy vitamin D [25(OH)D] concentration is the best indicator of vitamin D status, and determination of its deficiency or sufficiency. This level has high heritability (28-80%). However, genes contributing to the wide variation in serum 25(OH)D are generally unknown. In this study, we screened nine important genes in vitamin D metabolic pathways using 49 single nucleotide polymorphism (SNP) markers in a group of 156 unrelated healthy Caucasian subjects. Significant confounding factors that may affect serum 25(OH)D variations were used as covariates for the association analyses. An association test for quantitative trait was performed to evaluate the association between candidate genes and serum 25(OH)D levels. Permutation was conducted for correcting multiple testing problems. Evidence of association was observed at SNPs in the CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1) and the GC (vitamin D binding protein) gene. Next, we performed a replication study for six promising SNPs in the gene CYP2R1 and GC, using another group of 340 unrelated healthy Caucasian subjects. Association analyses were conducted in the replication cohort (n = 340) and the pooled cohort (n = 496). The CYP2R1 gene and the GC gene remain significant in the pooled cohort. The results suggest that the CYP2R1 and GC genes may contribute to the variation of serum 25(OH)D levels in healthy populations.