Association between PON 1 polymorphisms, PON activity and diabetes complications
Association between PON 1 polymorphisms, PON activity and diabetes complications
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DOI：
10.1016/j.jdiacomp.2005.08.008
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Donaghue, Kim C.
中科院分区：
文献类型：
--
作者：
Hofer, Sabine E.;Bennetts, Bruce;Donaghue, Kim C.
对氧磷酶（PON）基因簇定位于人类染色体7q21-22。在PON I基因中，已经确定了启动子和编码区的几个多态性，并且已知这些多态性会影响基因表达水平。启动子多态性已被证明对对氧磷酶活性水平有最强的影响。对氧磷酶是一种高密度脂蛋白相关酶，可保护脂蛋白免于氧化。脂质氧化可能在微血管和大血管疾病的发生中起重要作用。有证据表明糖尿病患者对氧磷酶活性降低。因此，我们假设PON I基因型影响对氧磷酶活性水平，并增加1型糖尿病微血管疾病的风险。对156名患有糖尿病的高加索青少年进行了7种PON I多态性的基因分型，其中包括一种新的PON I启动子多态性a (-1074)G。PON基因型与对氧磷酶和芳烯酯酶活性及糖尿病并发症有关。PON I启动子多态性之间存在强烈的连锁不平衡。启动子和编码区多态性都强烈影响活性水平，并与糖尿病并发症有关。PON 1基因型Leu/Leu 54、AA（-162）和GG（-1074）与尿白蛋白损失较高相关，而基因型GG（-907）对视网膜病变具有保护作用。(c) 2006爱思唯尔公司版权所有。
The paraoxonase (PON) gene cluster maps to human chromosome 7q21-22. In the PON I gene, several polymorphisms in the promoter and coding regions have been identified and are known to influence gene expression levels. Promoter polymorphisms have been shown to have the strongest influence on paraoxonase activity levels. Paraoxonase, a high-density lipoprotein associated enzyme, protects lipoproteins from oxidation. Lipid oxidation may play an important role in the development of micro- and macrovascular disease. There is evidence that paraoxonase activity is reduced in patients with diabetes. We therefore hypothesise that PON I genotypes influence paraoxonase activity levels and increase the risk of microvascular disease in type 1 diabetes. Genotyping of 156 Caucasian adolescents with diabetes for seven PON I polymorphisms was performed, including that of a novel PON I promoter polymorphism A(-1074)G. PON genotypes were related to paraoxonase and arylesterase activities and diabetes complication status. There was strong linkage disequilibrium between the PON I promoter polymorphisms. Both promoter and coding region polymorphisms strongly influenced activity levels and were associated with diabetes complications. PON 1 genotypes Leu/Leu 54, AA(-162) and GG(-1074) were associated with higher urinary albumin loss, while the genotype GG(-907) was protective for retinopathy. (c) 2006 Elsevier Inc. All rights reserved.