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首页> 外文期刊>The Review of Diabetic Studies : RDS >The rs11705701 G>A Polymorphism of IGF2BP2 is Associated With IGF2BP2 mRNA and Protein Levels in the Visceral Adipose Tissue - A Link to Type 2 Diabetes Susceptibility
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The rs11705701 G>A Polymorphism of IGF2BP2 is Associated With IGF2BP2 mRNA and Protein Levels in the Visceral Adipose Tissue - A Link to Type 2 Diabetes Susceptibility

机译：rs11705701 G> A IGF2BP2的多态性与内脏脂肪组织中的IGF2BP2 mRNA和蛋白水平相关联-与2型糖尿病易感性有关

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BACKGROUND: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) regulates translation of IGF2, a growth factor that plays a key role in controlling fetal growth and organogenesis including adipogenesis and pancreatic development. In Caucasians, the rs4402960 G>T polymorphism of IGF2BP2 has been shown to predispose to type 2 diabetes (T2D) in multiple populations. In this study, we tested whether rs4402960 G>T and rs11705701 G>A contribute to the development of T2D in a Russian population. METHODS: Both markers were genotyped in Russian diabetic (n = 1,470) and non-diabetic patients (n = 1,447) using a Taqman allele discrimination assay. The odds ratio (OR) for the risk of developing T2D was calculated using logistic regression assuming an additive genetic model adjusted for age, sex, HbA1c, hypertension, obesity, and body mass index (BMI). Multivariate linear regression analyses were used to test genotype-phenotype correlations, and adjusted for age, sex, hypertension, obesity, and BMI. Expression of IGF2BP2 in the visceral adipose tissue was quantified using real-time PCR. The content of IGF2BP2 protein and both its isoforms (p58 and p66) in the adipose tissue was measured using Western blot analysis. RESULTS: There was no significant association between rs4402960 and T2D. Whereas, allele A of rs11705701 was associated with higher T2D risk (OR = 1.19, p IGF2BP2 variants. Also, allele A of rs11705701 was associated with reduced amounts of the short isoform (p58) and increased levels of the long isoform (p66) of the IGF2BP2 protein in adipose tissue of non-obese diabetic and non-diabetic subjects. CONCLUSIONS: IGF2BP2 genetic variants contribute to insulin resistance in Russian T2D patients. The short protein isoform p58 of IGF2BP2 is likely to play an anti-diabetogenic role in non-obese individuals.
机译：背景：胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）调节IGF2的翻译，IGF2是一种在控制胎儿生长和器官形成（包括脂肪形成和胰腺发育）中起关键作用的生长因子。在高加索人中，IGF2BP2的rs4402960 G> T多态性已显示易患多种人群的2型糖尿病（T2D）。在这项研究中，我们测试了rs4402960 G> T和rs11705701 G> A是否有助于俄罗斯人口中T2D的发展。方法：使用塔克曼等位基因鉴别分析法对俄罗斯糖尿病患者（n = 1470）和非糖尿病患者（n = 1447）的两种标记物进行基因分型。假设针对年龄，性别，HbA1c，高血压，肥胖症和体重指数（BMI）进行了调整的附加遗传模型，则使用逻辑回归计算出发生T2D风险的比值比（OR）。多元线性回归分析用于检验基因型与表型的相关性，并针对年龄，性别，高血压，肥胖症和BMI进行了调整。使用实时PCR定量内脏脂肪组织中IGF2BP2的表达。使用蛋白质印迹分析测量脂肪组织中IGF2BP2蛋白及其两个同工型（p58和p66）的含量。结果：rs4402960与T2D之间没有显着关联。而rs11705701的等位基因A与较高的T2D风险相关（OR = 1.19，p IGF2BP2变体。此外，rs11705701的等位基因A与减少的短同工型（p58）和增加的长同工型（p66）相关。结论：IGF2BP2遗传变异有助于俄罗斯T2D患者的胰岛素抵抗; IGF2BP2的短蛋白同工型p58可能在非肥胖人群中具有抗糖尿病作用肥胖的个体。

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