Cai Guowen, Cole Shelley A, Tejero M Elizabeth, Proffitt John M, Freeland-Graves Jeanne H, Blangero John, Comuzzie Anthony G
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78227-5301, USA.
Obes Res. 2004 Nov;12(11):1766-72. doi: 10.1038/oby.2004.219.
Previous research has suggested a genetic contribution to the development of insulin resistance and obesity. We hypothesized that the same genes influencing insulin resistance might also contribute to the variation in adiposity.
A total of 601 (200 male, 401 female) adult baboons (Papio hamadryas) from nine families with pedigrees ranging in size from 43 to 121 were used in this study. Plasma insulin, glucose, C-peptide, and adiponectin were analyzed, and homeostasis model assessment of insulin resistance (HOMA IR) was calculated. Fat biopsies were collected from omental fat tissue, and triglyceride concentration per gram of fat tissue was determined. Body weight and length were measured, and BMI was derived. Univariate and bivariate quantitative genetic analyses were performed using SOLAR.
Insulin, glucose, C-peptide, and adiponectin levels, HOMA IR, triglyceride concentration of fat tissue, body weight, and BMI were all found to be significantly heritable, with heritabilities ranging from 0.15 to 0.80. Positive genetic correlations (r(G)s) were observed for HOMA IR with C-peptide (r(G) = 0.88 +/- 0.10, p = 0.01), triglyceride concentration in fat tissue (r(G) = 0.86 +/- 0.33, p = 0.02), weight (r(G) = 0.50 +/- 0.20, p = 0.03), and BMI (r(G) = 0.64 +/- 0.22, p = 0.02).
These results suggest that a set of genes contributing to insulin resistance also influence general and central adiposity phenotypes. Further genetic research in a larger sample size is needed to identify the common genes that constitute the genetic basis for the development of insulin resistance and obesity.
先前的研究表明基因对胰岛素抵抗和肥胖的发展有影响。我们假设影响胰岛素抵抗的相同基因也可能导致肥胖程度的差异。
本研究使用了来自9个家族的601只（200只雄性，401只雌性）成年狒狒（阿拉伯狒狒），家族谱系大小从43到121不等。分析了血浆胰岛素、葡萄糖、C肽和脂联素，并计算了胰岛素抵抗的稳态模型评估值（HOMA-IR）。从网膜脂肪组织采集脂肪活检样本，测定每克脂肪组织中的甘油三酯浓度。测量体重和体长，并计算体重指数（BMI）。使用SOLAR进行单变量和双变量定量遗传分析。
胰岛素、葡萄糖、C肽和脂联素水平、HOMA-IR、脂肪组织甘油三酯浓度、体重和BMI均显示出显著的遗传性，遗传率范围为0.15至0.80。观察到HOMA-IR与C肽（r(G)=0.88±0.10，p=0.01）、脂肪组织甘油三酯浓度（r(G)=0.86±0.33，p=0.02）、体重（r(G)=0.50±0.20，p=0.03）和BMI（r(G)=0.64±0.22，p=0.02）之间存在正遗传相关性。
这些结果表明，一组导致胰岛素抵抗的基因也影响全身和中心性肥胖表型。需要在更大样本量上进行进一步的基因研究，以确定构成胰岛素抵抗和肥胖发展遗传基础的共同基因。
