Association of the Vitamin D Metabolism Gene CYP24A1 With Coronary Artery Calcification

作者：Shen Haiqing; Bielak Lawrence F; Ferguson Jane F; Streeten Elizabeth A; Yerges Armstrong Laura M; Liu Jie; Post Wendy; O'; Connell Jeffery R; Hixson James E; Kardia Sharon L R; Sun Yan V; Jhun Min A; Wang Xuexia; Mehta Nehal N; Li Mingyao; Koller Daniel L; Hakonarson Hakan; Keating Brendan J; Rader Daniel J; Shuldiner Alan R; Peyser Patricia A; Reilly Muredach P; Mitchell Braxton D^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, 30(12): 2648-U587.

DOI：10.1161/ATVBAHA.110.211805

• calcification
• coronary artery disease
• epidemiology
• gene mutations
• vitamin D metabolism

Objective-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).
Methods and Results-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 comprising 697 Amish subjects, and SNPs nominally associated with CAC quantity (4 SNPs in CYP24A1, P = 0.008 to 0.00003) were then tested for association with CAC quantity in 2 independent cohorts of subjects of white European ancestry (Genetic Epidemiology Network of Arteriopathy study [n = 916] and the Penn Coronary Artery Calcification sample [n = 2061]). One of the 4 SNPs, rs2762939, was associated with CAC quantity in both the Genetic Epidemiology Network of Arteriopathy (P = 0.007) and Penn Coronary Artery Calcification (P = 0.01) studies. In all 3 populations, the rs2762939 C allele was associated with lower CAC quantity. Metaanalysis for the association of this SNP with CAC quantity across all 3 studies yielded a P value of 2.9 x 10(-6).
Conclusion-A common SNP in the CYP24A1 gene was associated with CAC quantity in 3 independent populations. This result suggests a role for vitamin D metabolism in the development of CAC quantity. (Arterioscler Thromb Vasc Biol. 2010;30:2648-2654.)

• 出版日期2010-12