Association between PON1 L/M55 polymorphism and plasma lipoproteins in two Canadian aboriginal populations
Association between PON1 L/M55 polymorphism and plasma lipoproteins in two Canadian aboriginal populations
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DOI：
10.1515/cclm.2000.060
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发表时间：
2000-05-01
影响因子：
6.8
通讯作者：
Hegele, RA
中科院分区：
文献类型：
--
作者：
Fanella, S;Harris, SB;Hegele, RA
血清对氧磷酶在高密度脂蛋白的亚组分上循环，似乎使用低密度和高密度脂蛋白颗粒上的磷脂作为生理底物。这种功能关系可以解释PON1基因（密码子55和192）的常见变异与动脉粥样硬化和脂蛋白代谢相关表型之间的关联。我们评估了两个加拿大土著人群（Oji-Cree和Inuit）的血浆脂蛋白与PON1 L/M55、PON1 Q/R192和PON2 A/G148多态性之间的关系。在糖尿病Oji-Cree中，我们发现PON1 M55携带者的平均血浆甘油三酯浓度高于非携带者。在非糖尿病Oji-Cree中，我们发现PON1 M55携带者的平均血浆总胆固醇和低密度脂蛋白胆固醇和载脂蛋白B浓度高于非携带者。在因纽特人中，我们发现PON1 M55携带者的平均血浆总脂蛋白和低密度脂蛋白胆固醇浓度高于非携带者。其他多态性标记与任何血浆脂蛋白性状的变异无关。因此，PON1 M55等位基因似乎与两个独立的加拿大原住民样本的血浆脂蛋白谱的有害变化有关。这些结果表明，PON1密码子55的共同变异与加拿大原住民血浆脂蛋白代谢中间性状的变异有关。
Serum paraoxonase circulates on a subfraction of high density lipoproteins and appears to use phospholipids on both low and high density lipoprotein particles as a physiological substrate. This functional relationship could explain the reported associations between common variation in the PON1 gene - at codons 55 and 192 - and phenotypes related to atherosclerosis and lipoprotein metabolism. We evaluated associations between plasma lipoproteins and PON1 L/M55, PON1 Q/R192 and PON2 A/G148 polymorphisms in samples from two Canadian aboriginal populations, namely the Oji-Cree and the Inuit. In diabetic Oji-Cree, we found that carriers of PON1 M55 had a higher mean plasma triglyceride concentration than non-carriers. In non-diabetic Oji-Cree, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoporetein cholesterol and apo B than non-carriers. in Inuit, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoprotein cholesterol than non-carriers. The other polymorphic markers were not associated with variation in any plasma lipoprotein trait. Thus, the PON1 M55 allele appeared to be associated with deleterious changes in the plasma lipoprotein profile from two independent Canadian aboriginal samples. These results suggest that common variation in PON1 codon 55 is associated with variation of intermediate traits in plasma lipoprotein metabolism in aboriginal Canadians.