Association of the 276G→T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans
Association of the 276G→T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans
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DOI：
10.1093/ajcn/82.4.760
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发表时间：
2005-10-01
影响因子：
7.1
通讯作者：
Ordovas, JM
中科院分区：
文献类型：
--
作者：
Jang, Y;Lee, JH;Ordovas, JM
目的：我们评估了脂联素基因变异是否与循环中的脂联素、胰岛素抵抗(IR)或心血管疾病的危险因素有关。设计：对非糖尿病受试者[n=902；x+/-SE年龄：42.5+/-0.53y；体重指数(BMI；单位：kg/m(2))：24.7+/-0.11]进行了45T>；G和276G-GT两个单核苷酸多态(SNPs)基因分型；结果：在调整了年龄、性别和BMI后，携带SNP 276 G等位基因的受试者的三酰甘油和小密度低密度脂蛋白(SdLDL)浓度显著高于TIT受试者，而低密度脂蛋白(LDL)颗粒尺寸明显小于TIT受试者。与T/T受试者相比，SNP 276位点GIG受试者的血浆脂联素水平显著降低，IR和尿前列腺素F2α的稳态模式评估(HOMA)显著升高。在SNP 45-276单倍型试验中，我们还观察到X/X单倍型受试者调整后血浆脂联素水平显著高于TG/TG或TG/X单倍型受试者。在最高体重指数组(BMI26)中，第276位SNP的TIT患者的HOMA-IR低于GIG或G/T组(P=0.011)，血浆脂联素高于GIG组或G/T组(P=0.026)。在单倍型人群中也可以看到脂联素的这些模式。结论：脂联素基因276G->多态对循环脂联素和胰岛素抵抗有调节作用，在肥胖人群中尤为明显。G等位基因携带者也有更高的氧化应激，更高的sdLDL浓度和更小的低密度脂蛋白颗粒尺寸。因此，脂联素基因276位点G等位基因的存在可能是韩国人心血管疾病风险增加的重要因素，而不受常见环境因素的影响。
Background: The adiponectin gene is known to modulate adiponectin concentrations and diabetes mellitus development.Objective: We assessed whether adiponectin gene variants contribute to circulating adiponectin, insulin resistance (IR), or cardiovascular disease risk factors.Design: Nondiabetic subjects [n = 902; x +/- SE age: 42.5 +/- 0.53 y; body mass index (BMI; in kg/m(2)) : 24.7 +/- 0.11] were genotyped for 2 single-nucleotide polymorphisms (SNPs), 45T -> G and 276G -> T.Results: 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 TIT subjects. GIG subjects at SNP 276 had significantly lower plasma adiponectin and higher homeostasis model assessment (HOMA) of IR and urinary prostaglandin F2 alpha 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 ! 26), TIT subjects had lower HOMA-IR (P = 0.011) and higher plasma adiponectin (P = 0.026) at SNP 276 than did GIG 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.Conclusions: 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.