Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification.
Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification.
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DOI：
10.1161/atvbaha.110.211805
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发表时间：
2010-12
期刊：
影响因子：
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通讯作者：
Mitchell BD
中科院分区：
文献类型：
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作者：
Shen H;Bielak LF;Ferguson JF;Streeten EA;Yerges-Armstrong LM;Liu J;Post W;O'Connell JR;Hixson JE;Kardia SL;Sun YV;Jhun MA;Wang X;Mehta NN;Li M;Koller DL;Hakonarson H;Keating BJ;Rader DJ;Shuldiner AR;Peyser PA;Reilly MP;Mitchell BD
维生素D内分泌系统对钙稳态至关重要，低水平的维生素D代谢产物与心血管疾病风险有关。我们假设调节维生素D代谢和信号通路的基因中的DNA序列变异可能会影响冠状动脉钙化（CAC）的变异。我们对GC、CYP 27 B1、CYP 24 A1和VDR的单核苷酸多态性（SNP）进行基因分型，并通过电子束计算机断层扫描检测其与CAC量的相关性。在由697名Amish受试者和名义上与CAC量相关的SNP组成的发现样本中进行了初步关联研究（CYP 24 A1中的4个SNP，P = 0.008-0.00003），然后在两个独立的欧洲高加索血统受试者队列中检验与CAC量的相关性（动脉病遗传流行病学网络（GENOA）研究（n = 916）和Penn冠状动脉钙化（PennCAC）样本（n = 2，061））。四个SNPs中的一个，rs 2762939，与GENOA（P = 0.007）和PennCAC（P = 0.01）中的CAC量相关。在所有三个群体中，rs 2762939 C等位基因与较低的CAC量相关。在所有三项研究中，对该SNP与CAC数量相关性的荟萃分析得出的P值为2.9 × 10-6。CYP 24 A1基因中一个常见的SNP与三个独立人群的CAC量相关。这一结果表明维生素D代谢在CAC量的发展中的作用。
The Vitamin D endocrine system is essential for calcium homeostasis, and low levels of vitamin D metabolites have been associated with cardiovascular disease risk. We hypothesized that DNA sequence variation in genes regulating vitamin D metabolism and signaling pathways might influence variation in coronary artery calcification (CAC). We genotyped single nucleotide polymorphisms (SNPs) in GC, CYP27B1, CYP24A1, and VDR and tested their association with CAC quantity, as measured by electron beam computed tomography. Initial association studies were carried out in a discovery sample comprised of 697 Amish subjects and SNPs nominally associated with CAC quantity (4 SNPs in CYP24A1, P = 0.008-0.00003) were then tested for association with CAC quantity in two independent cohorts of subjects of European Caucasian ancestry (Genetic Epidemiology Network of Arteriopathy (GENOA) Study (n = 916) and The Penn Coronary Artery Calcification (PennCAC) sample (n = 2,061)). One of the four SNPs, rs2762939, was associated with CAC quantity in both GENOA (P = 0.007) and PennCAC (P = 0.01). In all three populations the rs2762939 C allele was associated with lower CAC quantity. Meta-analysis for the association of this SNP with CAC quantity across all three studies yielded a P value of 2.9 × 10-6. A common SNP in the CYP24A1 gene was associated with CAC quantity in three independent populations. This result suggests a role for vitamin D metabolism in the development of CAC quantity.