Genomic insights into acute inflammatory lung injury
Genomic insights into acute inflammatory lung injury
复制标题
DOI：
10.1152/ajplung.00266.2006
复制
发表时间：
2006-12-01
影响因子：
4.9
通讯作者：
Vinasco, Liliana Moreno
中科院分区：
文献类型：
--
作者：
Garcia, Joe G. N.;Vinasco, Liliana Moreno
急性炎症性肺损伤的基因组见解。 Am J Physiol Lung Cell Mol Physiol 291：L1113-L1117，2006。首次发表于 2006 年 7 月 28 日； doi：10.1152/ajplung。 00266.2006.-急性肺损伤 (ALI) 是一种破坏性综合征（通常与脓毒症相关），是美国的主要医疗负担。我们的研究重点是利用候选基因方法来揭示该综合征的遗传基础，以确定 ALI 易感性的新基因。通过这种方法鉴定出的两个新基因包括前 B 细胞集落增强因子 (PBEF) 和肌球蛋白轻链激酶 (MLCK) 基因。人支气管肺泡灌洗液和 ALI 患者血清样本中的 PBEF 蛋白水平升高，DNA 测序发现了 PBEF 启动子中的两个单核苷酸多态性（T-1001G、C-1543T），这两个单核苷酸多态性在脓毒症诱发的 ALI 患者中出现过多。最近，我们发现 MLCK 单一多态性和单倍型与人类 ALI 相关，并在患有 ALI 的非洲裔美国人中观察到独特的变异。因此，基因组和遗传学方法代表了识别新候选基因和 ALI 治疗潜在靶标的强大策略。
Genomic insights into acute inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol 291: L1113-L1117, 2006. First published July 28, 2006; doi:10.1152/ajplung. 00266.2006.-Acute lung injury (ALI) is a devastating syndrome ( usually associated with sepsis) that represents a major healthcare burden in the United States. We have focused our studies on unraveling the genetic underpinnings of this syndrome utilizing a candidate gene approach to identify novel genes for ALI susceptibility. Two novel genes identified by this approach include pre-B cell colony-enhancing factor (PBEF) and the gene for myosin light chain kinase (MLCK). PBEF protein levels were elevated in human bronchoalveolar lavage and serum samples from patients with ALI, and DNA sequencing identified two single nucleotide polymorphisms in the PBEF promoter (T-1001G, C-1543T) that were over-represented in patients with sepsis-induced ALI. More recently, we found MLCK single polymorphisms and haplotypes to be associated with human ALI with unique variants observed in African-Americans with ALI. Thus genomic and genetic approaches represent powerful strategies in the identification of novel candidate genes and potential targets for ALI therapies.