Kim Kwang-Il, Na Jung-Eun, Kang Seo Young, Cho Young-Seok, Choi Dong-Ju, Kim Cheol-Ho, Kim Hyo-Soo, Oh Byung-Hee, Choi Yoon-Ho, Kwon In Soon, Park Sang-Chul
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Int J Cardiol. 2007 Dec 15;123(1):18-22. doi: 10.1016/j.ijcard.2006.11.105. Epub 2007 Feb 20.
Oxidative stress, the imbalance between production and removal of reactive oxygen species (ROS), is implicated in the process of cardiovascular aging. Membrane-associated NAD(P)H oxidase system is the most important source of ROS in vascular cells. p22(phox), a critical component of the NAD(P)H oxidase, has a polymorphic site on exon 4, associated with variable enzyme activity. The goal of this study is to investigate the effect of the p22(phox) C242T polymorphism on cardiovascular aging.
We investigated, in a cross-sectional study, the distribution of the p22(phox) genotypes and its impact on vascular aging in elderly Korean subjects (N=123, mean age+/-SD: 97.0+/-5.0). p22(phox) C242T polymorphism was determined by PCR and restriction fragment length polymorphism analysis. The p22(phox) genotype and allele frequencies were also compared with younger Korean subjects (N=363, mean age+/-SD: 49.0+/-10.3).
No significant difference was identified in p22(phox) genotype frequency according to the subject's age. However, the prevalence of CT+TT genotype was significantly less frequent in normotensive extremely elderly compared with younger subjects. Furthermore, the prevalence of the CT+TT genotype was significantly more frequent in hypertensive subjects (21.9%) than in the normotensive group (6.0%, P=0.016) in extremely elderly subject. The association was more significant in systolic hypertension rather than diastolic hypertension. Mean systolic blood pressure and pulse pressure were also significantly higher in subjects with CT+TT genotype. In contrast, there was no significant association between p22(phox) genotype and hypertension in younger-aged group.
These results suggest an association between the p22(phox) C242T polymorphism and vascular aging, which might be mediated by the increase of oxidative stress.
氧化应激，即活性氧（ROS）产生与清除之间的失衡，与心血管衰老过程有关。膜相关的NAD(P)H氧化酶系统是血管细胞中ROS的最重要来源。p22(phox)是NAD(P)H氧化酶的关键组成部分，其外显子4上有一个多态性位点，与酶活性的变化有关。本研究的目的是探讨p22(phox) C242T多态性对心血管衰老的影响。
在一项横断面研究中，我们调查了韩国老年受试者（N = 123，平均年龄±标准差：97.0±5.0）中p22(phox)基因型的分布及其对血管衰老的影响。通过聚合酶链反应（PCR）和限制性片段长度多态性分析确定p22(phox) C242T多态性。还将p22(phox)基因型和等位基因频率与年轻韩国受试者（N = 363，平均年龄±标准差：49.0±10.3）进行了比较。
根据受试者年龄，p22(phox)基因型频率未发现显著差异。然而，与年轻受试者相比，血压正常的极老年人中CT + TT基因型的患病率明显较低。此外，在极老年人中，高血压患者（21.9%）的CT + TT基因型患病率显著高于血压正常组（6.0%，P = 0.016）。这种关联在收缩期高血压中比在舒张期高血压中更显著。CT + TT基因型受试者的平均收缩压和脉压也显著更高。相比之下，在年轻组中，p22(phox)基因型与高血压之间没有显著关联。
这些结果表明p22(phox) C242T多态性与血管衰老之间存在关联，这可能是由氧化应激增加介导的。
