Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with Type II diabetes
Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with Type II diabetes
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DOI：
10.1007/s001250051481
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发表时间：
2000-08-01
期刊：
影响因子：
8.2
通讯作者：
Moulin, P
中科院分区：
文献类型：
--
作者：
Bernard, S;Touzet, S;Moulin, P
目的/假设。非酒精性脂肪性肝炎常见于II型（非胰岛素依赖型）糖尿病，可导致纤维化和肝硬化。然而，非酒精性脂肪性肝炎发生率的个体间差异表明存在遗传调节。微粒体甘油三酯转移蛋白（MTP）是VLDL组装和分泌所必需的，当蛋白质不起作用时，如无β脂蛋白血症，就会发生脂肪性肝炎。因此，我们评估了MTP基因启动子区（-493 G/T）功能多态性与II型糖尿病患者脂肪性肝炎生物学特征之间的关系。我们研究了271例II型糖尿病患者。采用PCR-RFLP方法检测-493 G/T多态性，以肝酶升高作为肝脂肪变性的替代指标，以丙氨酸氨基转移酶浓度作为多因素分析的结果变量。肝脏超声检查可用于新诊断的糖尿病患者亚组。GG亚组丙氨酸转氨酶升高的患者比例高于GT和TT亚组（分别为23%、11%和6%，p = 0.01）。此外，丙氨酸氨基转移酶浓度高的患者更可能是年轻（p = 0.01）、男性（p = 0.001）、肥胖（p = 0.04）和低HDL-胆固醇（p = 0.01）。在多变量分析中，MTP基因型与丙氨酸氨基转移酶浓度（p = 0.0023）以及性别和体重指数独立相关，但与HDL-胆固醇无关。-493 G/T MTP基因多态性与II型糖尿病患者脂肪性肝炎的生物学替代物相关导致MTP基因转录减少的G等位基因易于增加肝内甘油三酯含量，从而赋予脂肪性肝炎的遗传易感性。
Aims/hypothesis. Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients.Methods. We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP, Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes.Results. The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol.Conclusion/interpretation. The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.