Changes in whole blood gene expression in obese subjects with type 2 diabetes following bariatric surgery: a pilot study.
Changes in whole blood gene expression in obese subjects with type 2 diabetes following bariatric surgery: a pilot study.
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DOI：
10.1371/journal.pone.0016729
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发表时间：
2011-03-10
期刊：
影响因子：
3.7
通讯作者：
Smith JD
中科院分区：
文献类型：
--
作者：
Berisha SZ;Serre D;Schauer P;Kashyap SR;Smith JD
为了研究减肥手术对肥胖2型糖尿病患者全血基因表达谱的影响，进行了一项初步研究。11例肥胖2型糖尿病患者在减肥手术前和术后6-12个月分别在PAX基因管中采集全血。提取总RNA，扩增、标记后与Illumina基因表达芯片杂交。使用配对t检验分析临床和表达数据，并计算临床特征变化和转录本水平之间的相关性。使用Invenity Path分析和David基因本体论软件识别通路。总体而言，减肥手术显著降低了体重指数、空腹血糖、空腹胰岛素，并使糖化血红蛋白水平正常化。在减肥手术后，代表200个独特基因的204个转录本的表达水平发生了显著变化。在显著调控的基因中有GGT1、cAMP、DEFA1、Lcn2、TP53、PDSS1、OLR1、CNTNAP5、DHCR24、HHAT和SARDH，这些基因以前被认为与脂代谢、肥胖和/或2型糖尿病有关。选定的研究结果通过实时定量聚合酶链式反应进行复制。WDR35、FlF45244、DHCR24、TIGD7、TOPBP1、TSHZ1和FAM8A1七种转录本的表达变化与体重、空腹血糖和糖化血红蛋白含量的变化密切相关。与减肥手术后基因表达变化相关的主要途径是脂代谢、小分子生化和基因表达。两种抗菌肽是减肥手术后基因表达变化最大的转录本之一。这项初步研究的数据表明，特定转录本的全血表达水平可能有助于作为与2型糖尿病易感性和/或治疗反应相关的生物标记物。
A pilot study was performed in order to investigate the effects of bariatric surgery on whole blood gene expression profiles in obese subjects with type 2 diabetes. Whole blood from eleven obese subjects with type 2 diabetes was collected in PAXgene tubes prior to and 6–12 months after bariatric surgery. Total RNA was isolated, amplified, labeled and hybridized to Illumina gene expression microarrays. Clinical and expression data were analyzed using a paired t-test, and correlations between changes in clinical trait and transcript levels were calculated. Pathways were identified using Ingenuity Pathway Analysis and DAVID gene ontology software. Overall, bariatric surgery resulted in significant reduction of body mass index, fasting plasma glucose, fasting plasma insulin, and normalization of glycosylated hemoglobin levels. The expression levels of 204 transcripts, representing 200 unique genes, were significantly altered after bariatric surgery. Among the significantly regulated genes were GGT1, CAMP, DEFA1, LCN2, TP53, PDSS1, OLR1, CNTNAP5, DHCR24, HHAT and SARDH, which have been previously implicated in lipid metabolism, obesity and/or type 2 diabetes. Selected findings were replicated by quantitative real-time-PCR. The changes in expression of seven transcripts, WDR35, FLF45244, DHCR24, TIGD7, TOPBP1, TSHZ1, and FAM8A1 were strongly correlated with the changes in body weight, fasting plasma glucose and glycosylated hemoglobin content. The top pathways associated with gene expression changes after bariatric surgery was lipid metabolism, small molecule biochemistry and gene expression. Two antimicrobial peptides were among the transcripts with the largest changes in gene expression after bariatric surgery. Data from this pilot study suggest that whole blood expression levels of specific transcripts may be useful as biomarkers associated with susceptibility for type 2 diabetes and/or therapeutic response.
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DOI：
10.1016/j.jsbmb.2008.03.010
发表时间：
2008-04-01
影响因子：
4.1
作者：
Otis, Melissa;Battista, Marie-Claude;Gallo-Payet, Nicole
通讯作者：
Gallo-Payet, Nicole
影响因子：
16.2
作者：
Esteve E;Ricart W;Fernández-Real JM
通讯作者：
Fernández-Real JM
影响因子：
7.2
作者：
André, P;Balkau, B;Eschwège, E
通讯作者：
Eschwège, E
影响因子：
5.8
作者：
Manco, Melania;Fernandez-Real, J. Manuel;Mingrone, Geltrude
通讯作者：
Mingrone, Geltrude
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.