Tejero M Elizabeth, Proffitt J Michael, Cole Shelley A, Freeland-Graves Jeanne H, Cai Guowen, Peebles Kyle W, Cox Laura A, Mahaney Michael C, Rogers Jeffrey, Vandeberg John L, Blangero John, Comuzzie Anthony G
Department of Genetics, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227-5301, USA.
Obes Res. 2004 Oct;12(10):1652-7. doi: 10.1038/oby.2004.205.
Glucose transporter 4 (GLUT4) is an insulin-responsive glucose transporter expressed in adipose tissue. A decrease of the mRNA abundance of GLUT4 in adipose tissue has been observed in conditions of insulin resistance. The objective was to conduct quantitative genetic analyses using GLUT4 mRNA levels in omental adipose tissue of baboons as a novel phenotype.
A blood sample and a biopsy of omental adipose tissue were collected from 418 adult, pedigreed baboons. Total RNA was isolated from adipose tissue biopsies, and GLUT4 mRNA abundance was assayed by quantitative, real-time reverse transcription-polymerase chain reaction. Insulin and glucose were determined in fasting plasma by standard methods. Quantitative genetic analyses were conducted using GLUT4 mRNA, insulin, and glucose as quantitative traits.
GLUT4 mRNA expression in omental adipose tissue was heritable (h(2) = 0.23, p = 0.001). Bivariate genetic analyses revealed a significant genetic correlation (rho(G)) between GLUT4 mRNA abundance and both body weight (rho(G) = 0.63, p = 0.007), BMI (rho(G) = 0.59, p = 0.02) and insulin (rho(G) = 0.72, p = 0.04). A genome scan was conducted, and a quantitative trait locus was detected on chromosome 10p12 with a logarithm of the odds ratio score of 1.1.
GLUT4 mRNA abundance in omental adipose tissue has a significant genetic component. These findings suggest that expression of GLUT4 mRNA, plasma insulin levels, and body weight may be regulated by common genes.
葡萄糖转运蛋白4(GLUT4)是一种在脂肪组织中表达的胰岛素反应性葡萄糖转运蛋白。在胰岛素抵抗的情况下,已观察到脂肪组织中GLUT4的mRNA丰度下降。目的是使用狒狒网膜脂肪组织中的GLUT4 mRNA水平作为一种新的表型进行定量遗传分析。
从418只成年纯种狒狒中采集血样和网膜脂肪组织活检样本。从脂肪组织活检样本中分离总RNA,并通过定量实时逆转录聚合酶链反应测定GLUT4 mRNA丰度。通过标准方法测定空腹血浆中的胰岛素和葡萄糖。使用GLUT4 mRNA、胰岛素和葡萄糖作为数量性状进行定量遗传分析。
网膜脂肪组织中GLUT4 mRNA表达具有遗传性(h(2)=0.23,p=0.001)。双变量遗传分析显示,GLUT4 mRNA丰度与体重(rho(G)=0.63,p=0.007)、BMI(rho(G)=0.59,p=0.02)和胰岛素(rho(G)=0.72,p=0.04)之间存在显著的遗传相关性。进行了全基因组扫描,在10号染色体p12上检测到一个数量性状位点,其优势比分数的对数为1.1。
网膜脂肪组织中GLUT4 mRNA丰度具有显著的遗传成分。这些发现表明,GLUT4 mRNA的表达、血浆胰岛素水平和体重可能受共同基因调控。