Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I
Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I
复制标题
DOI：
10.1194/jlr.p900001-jlr200
复制
发表时间：
2009-06-01
影响因子：
6.5
通讯作者：
Hegele, Robert A.
中科院分区：
文献类型：
--
作者：
Rajakumar, Chandheeb;Ban, Matthew R.;Hegele, Robert A.
肉毒碱棕榈酰转移酶IA由CPT 1A编码，是脂肪酸代谢的关键调节因子。以前，功能丧失突变，即C。1436 C -> T（p.P479L），在CPT 1A纯合子状态下，在加拿大土著男性CPT 1A中报告，推测CPT 1A缺乏。为了确定这种变异的人口频率，我们确定了CPT 1A p.P479L基因型在1111格陵兰因纽特人。基因型与血浆总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、载脂蛋白（apo）B和apoA-I变异之间的关系也进行了研究。我们发现L479等位基因在该样本中以高频率（0.73）出现，而在285个非土著样本中完全缺失。这表明最初的先证者的症状不太可能是由于CPT 1A p.P479L突变，因为它在因纽特人中非常常见，并且因为提示CPT 1A缺乏症的症状在随后的研究中没有报告。然而，CPT 1A p.P479L与血浆HDL和apoA-I水平升高相关。与HDL和apoA-I水平升高的相关性表明，该多态性可能有助于预防动脉粥样硬化。Rajakumar，C.，M. R. Ban，H. Cao，T. K. Young，P. Bjerregaard，and R. A.海格勒肉毒碱棕榈酰转移酶IA多态性P479 L在格陵兰因纽特人中很常见，并与血浆载脂蛋白A-I升高相关。J. Lipid Res. 2009. 50：1223-1228。
Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty acid metabolism. Previously, a loss-of-function mutation, namely, c. 1436 C -> T (p. P479L), was reported in CPT1A in the homozygous state in Canadian aboriginal male with presumed CPT1A deficiency. To determine the population frequency of this variant, we determined CPT1A p. P479L genotypes in 1111 Greenland Inuit. Associations between genotype and variation in plasma total cholesterol, triglycerides, LDL, HDL, apolipoprotein (apo) B, and apoA-I was also investigated. We found the L479 allele occurs at a high frequency in this sample (0.73), while it was completely absent in 285 nonaboriginal samples. This suggests that the original proband's symptoms were not likely due to the CPT1A p. P479L mutation because it is very common in Inuit and because symptoms suggesting CPT1A deficiency have not been reported in any carrier subsequently studied. However, CPT1A p. P479L was associated with elevated plasma HDL and apoA-I levels. The association with increased levels of HDL and apoA-I suggest that the polymorphism might protect against atherosclerosis.-Rajakumar, C., M. R. Ban, H. Cao, T. K. Young, P. Bjerregaard, and R. A. Hegele. Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I. J. Lipid Res. 2009. 50: 1223-1228.