DNA sequence variation in human apolipoprotein C4 gene and its effect on plasma lipid profile
DNA sequence variation in human apolipoprotein C4 gene and its effect on plasma lipid profile
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DOI：
10.1016/s0021-9150(99)00459-1
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发表时间：
2000-09-01
期刊：
影响因子：
5.3
通讯作者：
Hamman, RF
中科院分区：
文献类型：
--
作者：
Kamboh, MI;Aston, CE;Hamman, RF
人载脂蛋白C-IV(apoC-IV，蛋白质；apoC4基因)是载脂蛋白E/C_1/C_2基因簇的新成员。在转基因小鼠中，人apoC-IV主要与极低密度脂蛋白(VLDL)相关，因此可能在脂质代谢中发挥重要作用。据我们所知，载脂蛋白C4基因变异的程度和性质及其在脂质代谢中的作用尚不清楚。在这项研究中，我们通过SSCP和DNA测序来评估APOC4的所有三个外显子及其两侧内含子序列是否存在遗传变异。共检测到5个点突变，其中2个位于外显子1的非编码区(A609G和G620A)，2个位于外显子2(密码子36和52)，1个位于外显子3(密码子96)。外显子2和3的三个突变预测了氨基酸替换，即Leu36Pro、Gly52Asp和Leu96Arg。变异等位基因频率为：609G为0.010,620A为0.039，Pro36为0.502，Asp52为0.003，Arg96为0.357。在包括NT在内的10对APOC4中有5对之间观察到显著的成对连锁不平衡。620/密码子36，NT。620/密码子96、密码子36/密码子52、密码子36/密码子96和密码子52/密码子96。一般线性模型分析显示，Leu36Pro和Leu96Arg多态与女性甘油三酯水平显著相关。这与载脂蛋白C-IV在甘油三酯代谢中的作用是一致的。载脂蛋白C4基因变异的特征可能导致识别载脂蛋白C-IV在脂代谢或其他生理途径中的特定作用。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
Human apolipoprotein C-IV (apoC-IV, protein; APOC4, gene) is a new member of the APO E/C1/C2 gene cluster. In transgenic mice, human apoC-IV is predominantly associated with very low-density lipoprotein (VLDL) and thus may play an important role in lipid metabolism. To our knowledge, the extent and nature of APOC4 genetic variation and its role in lipid metabolism are unknown. In this study we have assessed the presence of genetic variation in all three exons of APOC4 and their flanking intronic sequence by SSCP and DNA sequencing. A total of five point mutations were observed, including two in the non-coding part of exon 1 (A609G and G620A), two in exon 2 (codons 36 and 52) and one in exon 3 (codon 96). The three mutations in exons 2 and 3 predict amino acid substitutions, Leu36Pro, Gly52Asp, and Leu96Arg. The frequencies of the variant alleles were: 0.010 for 609G, 0.039 for 620A, 0.502 for Pro36, 0.003 for Asp52 and 0.357 for Arg96. Significant pairwise linkage disequilibrium was observed between five of the ten APOC4 pairs, including nt. 620/codon 36, nt. 620/codon 96, codon 36/codon 52, codon 36/codon 96 and codon 52/codon 96. A general linear model analysis reveled a significant association of the Leu36Pro and the Leu96Arg polymorphisms with triglyceride levels in women. This is consistent with the proposed role of apoC-IV in triglyceride metabolism. The characterization of APOC4 genetic variation may lead to the identification of a specific role of apoC-IV in lipid metabolism or in other physiologic pathways. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.