MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study.
MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study.
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DOI：
10.1186/s12881-015-0242-6
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发表时间：
2015-10-12
影响因子：
--
通讯作者：
Kuo KK
中科院分区：
文献类型：
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作者：
Hsiao PJ;Lee MY;Wang YT;Jiang HJ;Lin PC;Yang YH;Kuo KK
微粒体甘油三酯转运蛋白（MTP）在肝脏中起脂质化和组装含载脂蛋白B的脂蛋白的作用。它与肝脏分泌脂质调节血脂、动脉粥样硬化密切相关。例MTTP基因突变者以无β脂蛋白血症和显著的肝脂肪变性或肝硬化为特征。已经报道了与代谢综合征、高脂血症和脂肪性肝炎相关的几种MTTP多态性。我们推测，MTTP基因多态性的个体易感性可能改变了血脂的调节和非酒精性脂肪性肝病（NAFLD）形成的风险。1193例受试者（1087例男性和106例女性，平均年龄45.9 ± 8.9岁）的横断面人群入组，无公认的继发性高脂血症。检测空腹血脂、胰岛素、非酯化脂肪酸，并转换为胰岛素抵抗指数、胰岛素抵抗指数（HOMA-IR）和脂肪抵抗指数（Adipo-IR）。TaqMan法检测MTTP基因启动子-493G/T、E98 D、I128 T、N166 S和Q297 H 5个多态性位点。采用多元回归分析来估计它们对血脂和NAFLD风险的影响。评估显示对LDL-C和非HDL-C的不同影响，其依次由Q297 H多态性、胰岛素抵抗、体重指数和年龄确定。纯合子次要等位基因（297 H）携带者具有显著较低的LDL-C和非HDL-C，但NAFLD风险较高。297 H变体的分子建模显示出更高的自由能，可能是指不稳定的结构和功能序列。这些结果表明MTTP基因多态性可以调节血脂稳态，从而决定血脂水平和NAFLD的风险。MTTP 297 H多态性与年龄、胰岛素抵抗和BMI相互作用，降低血清含apoB的脂蛋白（LDL-C和non-HDL-C），但增加NAFLD形成的风险。本文的在线版本（doi：10.1186/s12881-015-0242-6）包含补充材料，可供授权用户使用。
Microsomal triglyceride transfer protein (MTP) works to lipidate and assemble the apoB-containing lipoproteins in liver. It closely links up the hepatic secretion of lipid to regulate serum lipid and atherosclerosis. Cases of MTTP gene mutation is characterized by abetalipoproteinemia and remarkable hepatic steatosis or cirrhosis. Several MTTP polymorphisms have been reported relating to metabolic syndrome, hyperlipidemia and steatohepatitis. We supposed the regulation of serum lipids and risk of non-alcoholic fatty liver disease (NAFLD) formation may be modified by individual susceptibility related to the MTTP polymorphisms. A cross-sectional population of 1193 subjects, 1087 males and 106 females mean aged 45.9 ± 8.9 years, were enrolled without recognized secondary hyperlipidemia. Fasting serum lipid, insulin, and non-esterified fatty acid were assessed and transformed to insulin resistance index, HOMA-IR and Adipo-IR. After ruling out alcohol abuser, non-alcoholic fatty liver disease (NAFLD) was diagnosed by abdominal ultrasound. Five common MTTP polymorphisms (promoter -493G/T, E98D, I128T, N166S, and Q297H) were conducted by TaqMan assay. Multivariate regression analysis was used to estimate their impact on serum lipid and NAFLD risk. Assessment revealed a differential impact on LDL-C and non-HDL-C, which were sequentially determined by the Q297H polymorphism, insulin resistance, body mass index and age. Carriers of homozygous minor allele (297H) had significantly lower LDL-C and non-HDL-C but higher risk for NAFLD. Molecular modeling of the 297H variant demonstrated higher free energy, potentially referring to an unstable structure and functional sequence. These results evidenced the MTTP polymorphisms could modulate the lipid homeostasis to determine the serum lipids and risk of NAFLD. The MTTP 297H polymorphism interacted with age, insulin resistance and BMI to decrease serum apoB containing lipoproteins (LDL-C and non-HDL-C) but increase the risk of NAFLD formation. The online version of this article (doi:10.1186/s12881-015-0242-6) contains supplementary material, which is available to authorized users.