Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer.
Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer.
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DOI：
10.1186/1741-7015-9-2
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发表时间：
2011-01-11
期刊：
影响因子：
9.3
通讯作者：
Hebbel RP
中科院分区：
文献类型：
--
作者：
Wei P;Milbauer LC;Enenstein J;Nguyen J;Pan W;Hebbel RP
健康差距和心血管疾病的高患病率仍然是困扰全球的健康挑战。这项研究探讨了影响血管内皮生物学的遗传差异可能是导致非洲裔美国人 (AA) 与白种人美国人 (CA) 相比心血管疾病和癌症负担增加的一个因素的可能性。从自我认定的健康 20 至 29 岁 AA (n = 21) 和 CA (n = 17) 中，我们建立了血液生长内皮细胞 (BOEC) 培养物并应用了微阵列分析。 BOEC 从未受到体内影响，其基因表达反映了培养条件（精心控制）和供体遗传学。微阵列的显着性分析确定了单个基因的差异表达。基因集富集分析检查了预定基因集的表达，这些基因集调查了与内皮生物学相关的九个生物系统。在错误发现率 (FDR) = 0 的高度严格阈值下，AA 中有 31 个单基因差异表达。 PSPH 表现出最大的倍数变化 (AA > CA)，但这完全是由隐藏在 PSPH 探针组中的同源物 (PSPHL) 造成的。其他显着不同的基因包括： AA > CA、SOS1、AMFR、FGFR3；对于 AA < CA、ARVCF、BIN3、EIF4B。还有更多（204 个基因的 221 个转录本）在 FDR <.05 的不太严格的阈值下差异表达。使用生物系统方法，我们发现 AA 与 CA 的剪切响应生物学显着不同，显示该系统内 46/157 个基因的表达明显增强（AA > CA）。这里涉及的许多基因在内皮生物学中具有重要作用。剪切应力反应是内皮功能和血管稳态的关键调节因子，AA 和 CA 之间可能有所不同。这些结果可能对内皮细胞在血管疾病（高血压、中风）和癌症（通过血管生成）中的作用产生直接影响。此外，它们也与我们的总体假设相一致，即源自祖先大陆的遗传影响可能会影响内皮细胞生物学，从而导致 AA 之间血管相关疾病负担的差异。这里使用的方法可以有效地弥补结构基因组学信息（例如疾病关联）与细胞功能和病理生理学之间的差距。
Health disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA). From self-identified, healthy, 20 to 29-year-old AA (n = 21) and CA (n = 17), we established cultures of blood outgrowth endothelial cells (BOEC) and applied microarray profiling. BOEC have never been exposed to in vivo influences, and their gene expression reflects culture conditions (meticulously controlled) and donor genetics. Significance Analysis of Microarray identified differential expression of single genes. Gene Set Enrichment Analysis examined expression of pre-determined gene sets that survey nine biological systems relevant to endothelial biology. At the highly stringent threshold of False Discovery Rate (FDR) = 0, 31 single genes were differentially expressed in AA. PSPH exhibited the greatest fold-change (AA > CA), but this was entirely accounted for by a homolog (PSPHL) hidden within the PSPH probe set. Among other significantly different genes were: for AA > CA, SOS1, AMFR, FGFR3; and for AA < CA, ARVCF, BIN3, EIF4B. Many more (221 transcripts for 204 genes) were differentially expressed at the less stringent threshold of FDR <.05. Using the biological systems approach, we identified shear response biology as being significantly different for AA versus CA, showing an apparent tonic increase of expression (AA > CA) for 46/157 genes within that system. Many of the genes implicated here have substantial roles in endothelial biology. Shear stress response, a critical regulator of endothelial function and vascular homeostasis, may be different between AA and CA. These results potentially have direct implications for the role of endothelial cells in vascular disease (hypertension, stroke) and cancer (via angiogenesis). Also, they are consistent with our over-arching hypothesis that genetic influences stemming from ancestral continent-of-origin could impact upon endothelial cell biology and thereby contribute to disparity of vascular-related disease burden among AA. The method used here could be productively employed to bridge the gap between information from structural genomics (for example, disease association) and cell function and pathophysiology.
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影响因子：
6.9
作者：
Basu, Analabha;Tang, Hua;Arnett, Donna;Gu, C. Charles;Mosley, Tom;Kardia, Sharon;Luke, Amy;Tayo, Bamidele;Cooper, Richard;Zhu, Xiaofeng;Risch, Neil
通讯作者：
Risch, Neil
影响因子：
3.5
作者：
Basu, Analabha;Tang, Hua;Risch, Neil J.
通讯作者：
Risch, Neil J.
影响因子：
8.3
作者：
BURT, VL;WHELTON, P;LABARTHE, D
通讯作者：
LABARTHE, D
DOI：
10.1073/pnas.131213698
发表时间：
2001-07-17
影响因子：
11.1
作者：
Cho, H;Wang, WR;Yan, DL
通讯作者：
Yan, DL
影响因子：
4.5
作者：
Deo, Rahul C.;Patterson, Nick;Reich, David
通讯作者：
Reich, David