Endokrinologie und Stoffwechsel, Medizinische Klinik III, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
J Clin Lipidol. 2013 Nov-Dec;7(6):610-4. doi: 10.1016/j.jacl.2013.09.006. Epub 2013 Sep 30.
Rare variants in the protein coding regions of the lipoprotein lipase (LPL) gene have been shown to be important in the development of hypertriglyceridemia.
The aim of this study was to determine whether rare variants in the 3' and 5' untranslated regions (UTRs) of the LPL gene are also associated with severe hypertriglyceridemia.
The DNA sequences of the 3' and 5' UTRs of the LPL gene of 63 patients with triglycerides > 875 mg/dL (10 mmol) and 69 probands with triglycerides below the 25th percentile for age and sex were determined. The sequence at the 5' end was extended to include 2 further elements (-702 to -666 and -468 to -430) shown to be associated with the control of LPL expression.
No statistically significant difference was found in the occurrence of rare mutations in either the 3' or the 5' UTRs between the 2 groups. Sequence analysis allowed the genotyping of 47 single nucleotide polymorphisms (SNPs) in the 3' UTR and 11 in the 5' UTR. Two groups of SNPs in the 3' UTR, based on allelic association, were statistically significantly associated with plasma triglycerides. Each of these groups contained SNPs in the target sequences for microRNAs. These findings were replicated in independently formed groups.
We provide genetic evidence that microRNAs may play a role in the expression of LPL and thus plasma triglyceride levels.
脂蛋白脂肪酶（LPL）基因编码区的罕见变异被认为在高甘油三酯血症的发生中起重要作用。
本研究旨在确定 LPL 基因 3'和 5'非翻译区（UTR）中的罕见变异是否也与严重高甘油三酯血症有关。
测定了 63 例甘油三酯>875mg/dL（10mmol）的患者和 69 例甘油三酯低于年龄和性别第 25 百分位数的对照者 LPL 基因 3'和 5'UTR 的 DNA 序列。5'端的序列扩展到包含另外两个与 LPL 表达调控相关的元件（-702 至-666 和-468 至-430）。
两组之间 3'或 5'UTR 中罕见突变的发生没有统计学显著差异。序列分析允许在 3'UTR 中对 47 个单核苷酸多态性（SNP）和 5'UTR 中的 11 个 SNP 进行基因分型。基于等位基因关联，3'UTR 中有两组 SNP 与血浆甘油三酯呈统计学显著相关。这些组都包含了 microRNA 的靶序列中的 SNP。这些发现被独立形成的组复制。
我们提供了遗传证据表明 microRNA 可能在 LPL 的表达及其对血浆甘油三酯水平的影响中发挥作用。
