Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Harwick Building 6-56, 200 1st Street SW, Rochester, MN 55905, United States.
Atherosclerosis. 2011 Jun;216(2):390-4. doi: 10.1016/j.atherosclerosis.2011.02.018. Epub 2011 Feb 18.
Polymorphisms within the ICAM1 structural gene have been shown to influence circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) but their relation to atherosclerosis has not been clearly established. We sought to determine whether ICAM1 SNPs are associated with circulating sICAM-1 concentration, coronary artery calcium (CAC), and common and internal carotid intima medial thickness (IMT).
3550 black and white Coronary Artery Risk Development in Young Adults (CARDIA) Study subjects who participated in the year 15 and/or 20 examinations and were part of the Young Adult Longitudinal Study of Antioxidants (YALTA) ancillary study were included in this analysis. In whites, rs5498 was significantly associated with sICAM-1 (p<0.001) and each G-allele of rs5498 was associated with 5% higher sICAM-1 concentration. In blacks, each C-allele of rs5490 was associated with 6% higher sICAM-1 level; this SNP was in strong linkage disequilibrium with rs5491, a functional variant. Subclinical measurements of atherosclerosis in either year 15 or year 20 were not significantly related to ICAM1 SNPs.
In CARDIA, ICAM1 DNA segment variants were associated with sICAM-1 protein level including the novel finding that levels differ by the functional variant rs5491. However, ICAM1 SNPs were not strongly related to either IMT or CAC. Our findings in CARDIA suggest that ICAM1 variants are not major early contributors to subclinical atherosclerosis.
已经表明,细胞间黏附分子-1(ICAM-1)结构基因内的多态性会影响可溶性细胞间黏附分子-1(sICAM-1)的循环水平,但它们与动脉粥样硬化的关系尚未明确确定。我们试图确定 ICAM1 单核苷酸多态性是否与循环 sICAM-1 浓度、冠状动脉钙(CAC)以及常见和颈内动脉内膜中层厚度(IMT)有关。
这项分析纳入了 3550 名参加了第 15 年和/或 20 年检查且属于青年抗氧化剂纵向研究(YALTA)辅助研究的黑人和白人冠状动脉风险发展在年轻人(CARDIA)研究对象。在白人中,rs5498 与 sICAM-1 显著相关(p<0.001),rs5498 的每个 G 等位基因与 sICAM-1 浓度增加 5%相关。在黑人中,rs5490 的每个 C 等位基因与 sICAM-1 水平增加 6%相关;该 SNP 与功能变体 rs5491 紧密连锁不平衡。在第 15 年或第 20 年的任何一年,动脉粥样硬化的亚临床测量与 ICAM1 SNP 均无显著相关性。
在 CARDIA 中,ICAM1 DNA 片段变体与 sICAM-1 蛋白水平相关,包括一个新的发现,即水平因功能变体 rs5491 而不同。然而,ICAM1 SNP 与 IMT 或 CAC 相关性不强。我们在 CARDIA 中的发现表明,ICAM1 变体不是亚临床动脉粥样硬化的主要早期因素。