Hospital Universitario Reina Sofía, Universidad de Córdoba and CIBER Fisiopatología Obesidad y Nutrición CIBEROBN, Instituto de Salud Carlos III, 14004 Córdoba, Spain.
Atherosclerosis. 2011 Jan;214(1):110-6. doi: 10.1016/j.atherosclerosis.2010.10.027. Epub 2010 Nov 3.
AIMS/HYPOTHESIS: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR).
Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS.
Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure.
CONCLUSIONS/INTERPRETATION: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.
目的/假设：TCF7L2 基因的变异可预测 2 型糖尿病（T2DM）的发生。我们研究了 TCF7L2 基因变异与代谢综合征（MetS）的临床特征（常先于 T2DM 发生）之间的关联，以及它们与非遗传因素（包括血浆饱和脂肪酸（SFA）浓度和胰岛素抵抗（IR））之间的相互作用。
在 450 例 MetS 患者中测定了空腹血脂谱、胰岛素敏感性、胰岛素分泌、人体测量学、血压和 TCF7L2 基因的 10 个基因变异。
几种单核苷酸多态性（SNP）表现出与 SFA 或 IR 无关的表型关联。携带 rs7903146 罕见 T 等位基因的个体以及与 rs7903146 连锁不平衡的其他三个 SNP 的携带者，其血压和胰岛素分泌较低。高 IR 和 rs7903146 的 T 等位基因的存在协同作用，定义了胰岛素分泌减少的个体。携带 rs290481 次要等位基因的个体表现出脂质谱改变，载脂蛋白 B、非酯化脂肪酸、胆固醇和富含甘油三酯的脂蛋白中的载脂蛋白 B 以及 LDL 胆固醇的血浆水平增加。携带 rs11196224 次要等位基因且血浆 SFA 水平较高的个体表现出促凝/促炎生物标志物升高、胰岛素分泌受损和 IR 增加，而携带 rs17685538 次要等位基因且血浆 SFA 水平较高的个体血压升高。
结论/解释：TCF7L2 基因中的 SNP 与 MetS 患者的胰岛素分泌、血压、血脂和凝血功能差异相关，并且可能受血浆 SFA 或 IR 的调节。
