An analysis of the association between the vitamin D pathway and serum 25‐hydroxyvitamin D levels in a healthy Chinese population
An analysis of the association between the vitamin D pathway and serum 25‐hydroxyvitamin D levels in a healthy Chinese population
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DOI：
10.1002/jbmr.1926
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发表时间：
2013-08
影响因子：
6.2
通讯作者：
Zeng Zhang;Jin-wei He;W. Fu;Chang-qing Zhang;Zhenlin Zhang
中科院分区：
文献类型：
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作者：
Zeng Zhang;Jin-wei He;W. Fu;Chang-qing Zhang;Zhenlin Zhang
维生素D缺乏症已被公认为全球主要的公共卫生问题。最近的研究表明，遗传因素可能在决定高加索人和非洲裔美国人血清25-羟基维生素D [25（OH）D]水平方面发挥重要作用。然而，导致中国人血清25（OH）D水平变化的基因尚不清楚。在这项研究中，我们使用96个单核苷酸多态性（SNP）标记在2897名无关的中国健康受试者中筛选了维生素D代谢途径中的15个关键基因。可能影响血清25（OH）D水平变异性的重要混杂因素被用作关联分析的协变量。对数量性状进行关联检验，以评估候选基因与血清25（OH）D水平之间的关联。在本研究中，GC、CYP 2 R1和DHCR 7/NADSYN 1的变异体和/或单倍型被鉴定为与25（OH）D水平相关。与缺乏风险等位基因的受试者相比，具有两种变体（GC-rs 4588和CYP 2 R1-rs 10766197）的三个或四个风险等位基因的受试者出现25（OH）D浓度低于20 ng/mL的机会增加（比值比2.121，95%置信区间1.586-2.836，p = 6.1 × 10−8）。风险等位基因的每一个额外拷贝与log-25（OH）D浓度降低0.12倍显著相关（p = 3.7 × 10−12）。GC rs705117-rs 2282679-rs 1491710的单倍型TGA，GC rs 842999-rs705120-rs 222040-rs 4588-rs7041-rs 10488854的单倍型GAGTAC，GC rs 1155563-rs 222029的单倍型CA，CYP 2 R1 rs7936142-rs 12794714-rs 2060793-rs 16930609单倍型AAGA是25（OH）D浓度降低的遗传危险因素。而DHCR 7/NADSYN 1 rs 1790349-rs7122671-rs 1790329-rs 11606033-rs 2276360-rs 1629220-rs 2282618单倍型TGGGCCC则为保护性基因。结果提示，GC、CYP 2 R1和DHCR 7/NADSYN 1基因可能与上海地区健康人群血清25（OH）D水平的变异有关。这些标记物可用作维生素D孟德尔随机化分析的工具，它们可能成为上海中国人群的药物靶点。
Vitamin D deficiency has been recognized as a major public health issue worldwide. Recent studies have indicated that genetic factors might play an important role in determining serum 25‐hydroxyvitamin D [25(OH)D] levels in Caucasians and African Americans. However, the genes that contribute to the variation in serum 25(OH)D levels in Chinese are unknown. In this study, we screened 15 key genes within the vitamin D metabolic pathway using 96 single‐nucleotide polymorphism (SNP) markers in a group of 2897 unrelated healthy Chinese subjects. Significant confounding factors that may influence the variability in serum 25(OH)D levels were used as covariates for association analyses. An association test for quantitative traits was performed to evaluate the association between candidate genes and serum 25(OH)D levels. In the present study, variants and/or haplotypes in GC, CYP2R1, and DHCR7/NADSYN1 were identified as being associated with 25(OH)D levels. Participants with three or four risk alleles of the two variants (GC‐rs4588 and CYP2R1‐rs10766197) had an increased chance of presenting with a 25(OH)D concentration lower than 20 ng/mL (odds ratio 2.121, 95% confidence interval 1.586–2.836, p = 6.1 × 10−8) compared with those lacking the risk alleles. Each additional copy of a risk allele was significantly associated with a 0.12‐fold decrease in the log‐25(OH)D concentration (p = 3.7 × 10−12). Haplotype TGA of GC rs705117‐rs2282679‐rs1491710, haplotype GAGTAC of GC rs842999‐rs705120‐rs222040‐rs4588‐rs7041‐rs10488854, haplotype CA of GC rs1155563‐rs222029, and haplotype AAGA of CYP2R1 rs7936142‐rs12794714‐rs2060793‐rs16930609 were genetic risk factors toward a lower 25(OH)D concentration. In contrast, haplotype TGGGCCC of DHCR7/NADSYN1 rs1790349‐rs7122671‐rs1790329‐rs11606033‐rs2276360‐rs1629220‐rs2282618 were genetic protective factors. The results suggest that the GC, CYP2R1, and DHCR7/NADSYN1 genes might contribute to variability in the serum 25(OH)D levels in a healthy Chinese population in Shanghai. These markers could be used as tools in Mendelian randomization analyses of vitamin D, and they could potentially be drug targets in the Chinese population in Shanghai.