Mannino Gaia Chiara, Greco Annalisa, De Lorenzo Carlo, Andreozzi Francesco, Marini Maria A, Perticone Francesco, Sesti Giorgio
Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.
PLoS One. 2013 Dec 31;8(12):e85483. doi: 10.1371/journal.pone.0085483. eCollection 2013.
A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance.
METHODOLOGY/PRINCIPAL FINDINGS: Two samples of adult nondiabetic white Europeans were studied. In sample 1 (n=569), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (190±77 vs. 218±97 ng/ml, respectively; P=0.007 after adjusting for age, gender, and BMI). Insulin sensitivity assessed by euglycaemic-hyperinsulinemic clamp was lower in GG genotype carriers compared with A allele carriers (8.9±4.1 vs. 10.1±5.1 mg x Kg(-1) free fat mass x min(-1), respectively; P=0.03 after adjusting for age, gender, and BMI). The rs35767 polymorphism did not show significant association with insulin clearance. In sample 2 (n=859), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (155±60 vs. 164±63 ng/ml, respectively; P=0.02 after adjusting for age, gender, and BMI). Insulin sensitivity, as estimated by the HOMA index, was lower in GG genotype carriers compared with A allele carriers (2.8±2.2 vs. 2.5±1.3, respectively; P=0.03 after adjusting for age, gender, and BMI).
CONCLUSION/SIGNIFICANCE: The rs35767 polymorphism near IGF1 was associated with circulating IGF-1 levels, and insulin sensitivity with carriers of the GG genotype exhibiting lower IGF-1 concentrations and insulin sensitivity as compared with subjects carrying the A allele.
一项全基因组数据的荟萃分析报告称，在IGF1附近发现了rs35767多态性，其与空腹胰岛素水平存在全基因组显著关联。然而，尚不清楚该多态性对空腹胰岛素的影响是由胰岛素敏感性降低还是胰岛素清除受损介导的。我们研究了rs35767多态性对循环IGF-1水平、胰岛素敏感性和胰岛素清除的影响。
方法/主要发现：对成年非糖尿病白种欧洲人进行了两个样本的研究。在样本1（n = 569）中，与A等位基因携带者相比，GG基因型携带者的IGF-1水平较低（分别为190±77 vs. 218±97 ng/ml；校正年龄、性别和BMI后P = 0.007）。通过正常血糖高胰岛素钳夹评估的胰岛素敏感性，GG基因型携带者低于A等位基因携带者（分别为8.9±4.1 vs. 10.1±5.1 mg x Kg(-1) 无脂体重x min(-1)；校正年龄、性别和BMI后P = 0.03）。rs35767多态性与胰岛素清除无显著关联。在样本2（n = 859）中，与A等位基因携带者相比，GG基因型携带者的IGF-1水平较低（分别为155±60 vs. 164±63 ng/ml；校正年龄、性别和BMI后P = 0.02）。根据HOMA指数估计，GG基因型携带者的胰岛素敏感性低于A等位基因携带者（分别为2.8±2.2 vs. 2.5±1.3；校正年龄、性别和BMI后P = 0.03）。
结论/意义：IGF1附近的rs35767多态性与循环IGF-1水平和胰岛素敏感性相关，与携带A等位基因的受试者相比，GG基因型携带者的IGF-1浓度和胰岛素敏感性较低。
