Jang Yangsoo, Lee Jong Ho, Chae Jey Sook, Kim Oh Yoen, Koh Soo Jeong, Kim Ji Young, Cho Hongkeun, Lee Jong Eun, Ordovas Jose M
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, Korea.
Am J Clin Nutr. 2005 Oct;82(4):760-7. doi: 10.1093/ajcn/82.4.760.
The adiponectin gene is known to modulate adiponectin concentrations and diabetes mellitus development.
We assessed whether adiponectin gene variants contribute to circulating adiponectin, insulin resistance (IR), or cardiovascular disease risk factors.
Nondiabetic subjects [n = 902; x +/- SE age: 42.5 +/- 0.53 y; body mass index (BMI; in kg/m2): 24.7 +/- 0.11] were genotyped for 2 single-nucleotide polymorphisms (SNPs), 45T-->G and 276G-->T.
After adjustment for age, sex, and BMI, subjects with the G allele for the SNP 276 had significantly higher concentrations of triacylglycerol and small dense LDL (sdLDL) and smaller LDL particle size than did T/T subjects. G/G subjects at SNP 276 had significantly lower plasma adiponectin and higher homeostasis model assessment (HOMA) of IR and urinary prostaglandin F2alpha than did T/T subjects. In the SNP 45-276 haplotype test, we also observed that subjects with the X/X haplotype had significantly higher plasma adiponectin after adjustment than did TG/TG or TG/X haplotype subjects. In the highest BMI group (BMI > or = 26), T/T subjects had lower HOMA-IR (P = 0.011) and higher plasma adiponectin (P = 0.026) at SNP 276 than did G/G or G/T subjects. These patterns were also seen for adiponectin in haplotype groups. However, no significant genotype effect for SNP 45T-->G was observed.
The 276G-->T polymorphism of the adiponectin gene modulates circulating adiponectin and IR, particularly in obese states. G allele carriers also have higher oxidative stress, higher sdLDL concentrations, and smaller LDL particle size. Therefore, the presence of the G allele in the adiponectin gene at SNP 276 could be a significant contributor to higher cardiovascular disease risk in Koreans, independent of common environmental factors.
已知脂联素基因可调节脂联素浓度及糖尿病的发展。
我们评估了脂联素基因变异是否与循环脂联素、胰岛素抵抗（IR）或心血管疾病风险因素有关。
对非糖尿病受试者[n = 902；平均年龄±标准误：42.5±0.53岁；体重指数（BMI；单位：kg/m²）：24.7±0.11]进行了两个单核苷酸多态性（SNP），即45T→G和276G→T的基因分型。
在对年龄、性别和BMI进行校正后，SNP 276的G等位基因携带者的三酰甘油和小而密低密度脂蛋白（sdLDL）浓度显著高于T/T受试者，且低密度脂蛋白颗粒尺寸更小。SNP 276的G/G受试者的血浆脂联素显著低于T/T受试者，胰岛素抵抗的稳态模型评估（HOMA）及尿前列腺素F2α水平更高。在SNP 45 - 276单倍型检测中，我们还观察到，校正后X/X单倍型受试者的血浆脂联素显著高于TG/TG或TG/X单倍型受试者。在最高BMI组（BMI≥26）中，SNP 276处T/T受试者的HOMA-IR低于G/G或G/T受试者（P = 0.011），血浆脂联素高于G/G或G/T受试者（P = 0.026）。在单倍型组中脂联素也呈现出这些模式。然而，未观察到SNP 45T→G有显著的基因型效应。
脂联素基因的276G→T多态性可调节循环脂联素和IR，尤其是在肥胖状态下。G等位基因携带者还具有更高的氧化应激、更高的sdLDL浓度和更小的低密度脂蛋白颗粒尺寸。因此，SNP 276处脂联素基因中G等位基因的存在可能是韩国人心血管疾病风险升高的一个重要因素，且独立于常见环境因素。
