Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme
Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme
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DOI：
10.1017/s1751731109991145
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发表时间：
2010-02-01
期刊：
影响因子：
3.6
通讯作者：
Pena, R. N.
中科院分区：
文献类型：
--
作者：
Canovas, A.;Quintanilla, R.;Pena, R. N.
3-羟基-3-甲基戊二酰辅酶a还原酶（HMGCR）是胆固醇生物合成中的限速酶。我们通过表达和结构分析研究了HMGCR基因在猪脂质代谢中的作用。我们在这里描述了该基因在猪的完整编码区，并报告了编码区两个同义的单核苷酸多态性。此外，我们还研究了这些多态性之一（HMGCR: C .807 a >C）与杜洛克商业品系产生的半同胞群体中几种脂质沉积和胆固醇相关性状的关系，显示在一些家庭中HMGCR: C呈正相关。807A等位基因与血清低密度脂蛋白（LDL）结合胆固醇和甘油三酯水平以及臀中肌肌内脂肪（IMF）含量有关。我们还评估了68个杜洛克个体肌肉和肝脏中的表达水平，这些个体对应于分析特征的最极端动物。肝脏HMGCR表达量与血清高密度脂蛋白（HDL）水平、胴体瘦肉率和硬脂酸含量呈负相关，肌肉HMGCR表达量与胴体瘦肉率、硬脂酸和亚油酸含量呈负相关，与血清脂质胆固醇（HDL、LDL和总胆固醇）、IMF、肌肉油酸和棕榈酸含量呈正相关。有了这些信息，我们对表达数据与脂质代谢表型水平和HMGCR基因型进行了关联分析。结果表明，在脂肪沉积和总胆固醇水平极值的两组猪中，肌肉中HMGCR的表达水平存在差异，不同HMGCR基因型的动物之间也存在差异。
The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme in the biosynthesis of cholesterol. We have studied the role of the HMGCR gene in pig lipid metabolism by means of expression and structural analysis. We describe here the complete coding region of this gene in pigs and report two synonymous single nucleotide polymorphisms in the coding region. We have, additionally, studied the association of one of these polymorphisms (HMGCR:c.807A>C) with several lipid deposition- and cholesterol-related traits in a half-sib population generated from a commercial Duroc line, showing in some families a positive relationship of HMGCR:c.807A allele with serum low-density lipoprotein (LDL)-bound cholesterol and triglyceride levels, and also with intramuscular fat (IMF) content of gluteus medius muscle. We have also assessed the expression levels in muscle and in liver from 68 Duroc individuals corresponding to the most extreme animals for the analysed traits. Liver HMGCR expression correlated negatively with the serum high-density lipoprotein (HDL) levels, carcass lean percentage and stearic acid content while muscle expression correlated also negatively with the carcass lean percentage, stearic and linoleic acids content, but showed a positive correlation with the serum lipid cholesterol (HDL, LDL and total cholesterol), IMF and muscle oleic and palmitic fatty acid content. With this information, we have performed an association analysis of expression data with lipid metabolism phenotypic levels and the HMGCR genotype. The results indicate that HMGCR expression levels in muscle are different in the two groups of pigs with extreme values for fat deposition and total cholesterol levels, and also between animals with the different HMGCR genotypes.