Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians
Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians
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DOI：
10.1038/sj.ejhg.5200806
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发表时间：
2002-05-01
影响因子：
5.2
通讯作者：
Franceschi, C
中科院分区：
文献类型：
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作者：
Bonafè, M;Marchegiani, F;Franceschi, C
人对氧磷酶 (PON1) 是一种高密度脂蛋白 (HDL) 相关酯酶，可水解脂质过氧化物。 PON1作为一种针对LDL氧化修饰的保护因子最近引起了人们的关注，因此可能在预防动脉粥样硬化过程中发挥重要作用。两种多态性已得到广泛研究：密码子 55 处的亮氨酸（L 等位基因）替换为蛋氨酸（M 等位基因），以及密码子 192 处的谷氨酰胺（A 等位基因）替换为精氨酸（B 等位基因）。我们检查了 579 名 20 至 65 岁的人和 308 名百岁老人的这两种氨基酸变化。我们发现百岁老人中密码子192（B+个体）携带B等位基因的比例高于对照组（0.539 vs 0.447），而且我们发现在B+个体中，这种现象是由于密码子55位点携带M等位基因的人增加所致。总之，我们认为 PON1 基因座的遗传变异会影响高龄患者的生存。
Human Paraoxonase (PON1) is a High-Density Lipoprotein (HDL)-associated esterase that hydrolyses, lipo-peroxides. PON1 has recently attracted attention as a protective factor against oxidative modification of LDL and may therefore play an important role in the prevention of the atherosclerotic process. Two polymorphisms have been extensively studied: a Leucine (L allele) to Methionine (M allele) substitution at codon 55, and a Glutamine (A allele) to Arginine (B allele) substitution at codon 192. We have examined these two aminoacidic changes in 579 people aged 20 to 65 years old, and 308 centenarians. We found that the percentage of carriers of the B allele at codon 192 (B+ individuals) is higher in centenarians than in controls (0.539 vs 0.447), moreover we found that among the B+ individuals, the phenomenon was due to an increase of people carrying M alleles at codon 55 locus. In conclusion, we propose that genetic variability at PON1 locus affects survival at extreme advanced age.