Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS Genet. 2011 Apr;7(4):e1001374. doi: 10.1371/journal.pgen.1001374. Epub 2011 Apr 21.
Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4 × 10(-9)), PNPLA3 (rs738409, P = 5.8 × 10(-9)), RELA (rs1049728, P = 2.7 × 10(-16)), and SH2B3 (rs3184504, P = 2.9 × 10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.
可溶性细胞间黏附分子-1（sICAM-1）是一种内皮细胞衍生的炎症标志物，与多种疾病相关，如心肌梗死、糖尿病、中风和疟疾。尽管有证据表明 sICAM-1 水平具有遗传成分，但迄今为止只确定了少数遗传位点。为了全面解决这个问题，我们对来自女性基因组健康研究的 22435 名看似健康的女性的 sICAM-1 浓度进行了全基因组关联分析。虽然我们的结果证实了先前在 ABO 和 ICAM1 基因座报道的关联，但在 NFKBIK（rs3136642，P=5.4×10(-9)）、PNPLA3（rs738409，P=5.8×10(-9)）、RELA（rs1049728，P=2.7×10(-16)）和 SH2B3（rs3184504，P=2.9×10(-17)）附近发现了四个新的关联。两个基因座 NFKBIB 和 RELA 参与 NFKB 信号通路；PNPLA3 与脂肪肝疾病有关；SH3B2 与多种性状和疾病相关，包括心肌梗死。这些关联提供了对 sICAM-1 水平遗传调控的深入了解，并暗示这些基因座参与了内皮功能的调节。
