Hasselwander O, Savage D A, McMaster D, Loughrey C M, McNamee P T, Middleton D, Nicholls D P, Maxwell A P, Young I S
School of Clinical Medicine, The Queen's University of Belfast, Northern Ireland.
Kidney Int. 1999 Jul;56(1):289-98. doi: 10.1046/j.1523-1755.1999.00521.x.
Paraoxonase (PON1) gene variants have been identified as risk factors for cardiovascular disease (CVD). There are two common PON1 polymorphisms at position 55 (Leu-Met change) and 192 (Gln-Arg change) of the amino acid chain. Leucine at position 55 and arginine at position 192 have been associated with increased cardiovascular risk. The increased prevalence of CVD in renal transplant recipients can be only partly explained by the increased prevalence of conventional risk factors.
We therefore investigated PON1 polymorphisms in renal transplant recipients (N = 491) with (N = 103) and without CVD (N = 388) using polymerase chain reaction-restriction fragment length analysis. PON1 polymorphisms and their associated PON1/arylesterase activities were also assessed in a subgroup of patients (N = 165).
The genotype distribution and allele frequencies for both polymorphisms were similar in both groups. The frequencies for LL, LM, and MM genotypes for the 55 position in patients with CVD were 0.39, 0.51, and 0.10, respectively, compared with 0.43, 0.43, and 0.14 in patients without CVD (P = 0.31). The distribution for the QQ, QR, and RR genotypes at the 192 position were 0.48, 0.43, and 0.09, respectively, in patients with CVD compared with 0.46, 0.46, and 0.08 in patients without CVD (P = 0.8). There were highly significant differences in serum activities of PON1/arylesterase between genotypes defined by 55 and 192 polymorphisms. Leucine at position 55 and arginine at position 192 were associated with higher activities.
These data indicate that there is no association between the PON1 gene variants, conferring higher enzyme activity, and the increased cardiovascular risk in renal transplant recipients.
对氧磷酶（PON1）基因变异已被确定为心血管疾病（CVD）的危险因素。在氨基酸链的第55位（亮氨酸-甲硫氨酸改变）和第192位（谷氨酰胺-精氨酸改变）存在两种常见的PON1多态性。第55位的亮氨酸和第192位的精氨酸与心血管风险增加有关。肾移植受者中CVD患病率的增加仅部分可由传统危险因素患病率的增加来解释。
因此，我们使用聚合酶链反应-限制性片段长度分析法，对有CVD（n = 103）和无CVD（n = 388）的肾移植受者（n = 491）进行了PON1多态性研究。还在一组患者（n = 165）中评估了PON1多态性及其相关的PON1/芳基酯酶活性。
两组中两种多态性的基因型分布和等位基因频率相似。CVD患者中第55位的LL、LM和MM基因型频率分别为0.39、0.51和0.10，无CVD患者中分别为0.43、0.43和0.14（P = 0.31）。CVD患者中第192位的QQ、QR和RR基因型分布分别为0.48、0.43和0.09，无CVD患者中分别为0.46、0.46和0.08（P = 0.8）。由第55位和第192位多态性定义的基因型之间，PON1/芳基酯酶的血清活性存在高度显著差异。第55位的亮氨酸和第192位的精氨酸与较高活性相关。
这些数据表明，赋予较高酶活性的PON1基因变异与肾移植受者心血管风险增加之间无关联。
