A Promoter Polymorphism in the Liver-specific Fatty Acid Transport Protein 5 is Associated with Features of the Metabolic Syndrome and Steatosis
A Promoter Polymorphism in the Liver-specific Fatty Acid Transport Protein 5 is Associated with Features of the Metabolic Syndrome and Steatosis
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DOI：
10.1055/s-0030-1267186
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发表时间：
2010-11-01
影响因子：
2.2
通讯作者：
Rubin, D.
中科院分区：
文献类型：
--
作者：
Auinger, A.;Valenti, L.;Rubin, D.
脂肪酸转运蛋白5（FATP 5）仅在肝脏中表达，并参与肝脏脂质和胆汁代谢。我们研究了FATP 5启动子（rs56225452）的变异是否与肝脂肪变性和代谢综合征的进一步特征相关。对来自代谢干预队列基尔（MICK）的716名男性受试者和103名经组织学证实的非酒精性脂肪性肝病（NAFLD）男性受试者进行了FATP 5多态性rs56225452基因分型和代谢综合征特征表型。在MICK队列中，与GG纯合子相比，携带罕见A等位基因的受试者的ALT活性、餐后胰岛素和甘油三酯浓度更高。因此，A等位基因携带者在混合餐和标准化葡萄糖负荷后测定的胰岛素敏感性指数较低。携带等位基因A的NAFLD病例也表现出较高的ALT活性。在NAFLD受试者中，BMI与脂肪变性程度和葡萄糖浓度的相关性在FATP 5启动子多态性之间存在差异。FATP5启动子多态性rs56225452与一般人群中较高的ALT活性、胰岛素抵抗和血脂异常相关。在NAFLD病例中，BMI对脂肪变性严重程度的影响似乎取决于FATP 5多态性。
The fatty acid transport protein 5 (FATP5) is exclusively expressed in the liver and is involved in hepatic lipid and bile metabolism. We investigated whether a variation in the FATP5 promoter (rs56225452) is associated with hepatic steatosis and further features of the metabolic syndrome. A total of 716 male subjects from the Metabolic Intervention Cohort Kiel (MICK) and 103 male subjects with histologically proved nonalcoholic fatty liver disease (NAFLD) were genotyped for this FATP5 polymorphism rs56225452 and phenotyped for features of the metabolic syndrome. In the MICK cohort, ALT activities, postprandial insulin, and triglyceride concentrations were higher in subjects carrying the rare A-allele compared to GG homozygotes. Accordingly, the insulin sensitivity index determined after a mixed meal and standardized glucose load was lower in A-allele carriers. NAFLD cases carrying allele A were presented with also higher ALT activities. In NAFLD subjects, the association of BMI with the degree of steatosis and glucose concentration differed across FATP5 promoter polymorphism. The FATP5 promoter polymorphism rs56225452 is associated with higher ALT activity, insulin resistance, and dyslipidemia in the general population. The impact of the BMI on the severity of steatosis in NAFLD cases seems to depend on the FATP5 polymorphism.