Assareh Amelia A, Mather Karen A, Crawford John D, Wen Wei, Anstey Kaarin J, Easteal Simon, Tan Xiaoyun, Mack Holly A, Kwok John B J, Schofield Peter R, Sachdev Perminder S
Neuroscience Research Australia, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Collaborative Research Network for Mental Health and Well-being, University of New England, Armidale, Australia;
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia;
Am J Hypertens. 2014 Sep;27(9):1191-8. doi: 10.1093/ajh/hpu035. Epub 2014 Mar 12.
White matter lesions (WMLs), seen as hyperintensities on T2-weighted magnetic resonance imaging brain scans, are common in the brains of healthy older individuals. They are thought to be related to cerebral small vessel disease and to have a genetic component to their aetiology, and hypertension is thought to be an important risk factor. Genetic polymorphisms in hypertension-related genes may therefore be associated with the formation of WMLs.
In this study, a sample of 445 Australians aged 60-65 years was drawn from a larger longitudinal epidemiological study, the Personality and Total Health Through Life Project. The associations of single nucleotide polymorphisms (SNPs) in the genes encoding angiotensinogen (AGT, rs699), angiotensin-converting enzyme (ACE, rs4362), and angiotensin II receptor type 1 (AGTR1, rs5182) with WMLs were examined.
No individual SNPs showed a significant association with WMLs for the whole sample. When the cohort was stratified by sex, ACE rs4362 and AGT rs699 showed significant associations with WMLs in men only (P = 0.01 and P = 0.03, respectively), and remained significant after controlling for hypertension. Although the AGTR1 SNP did not show any association with WMLs, the interaction of the AGT rs699 and AGTR1 rs5182 SNPs with WMLs was significant before (P = 0.03) and after adjustment for hypertension (P = 0.045).
The results provide evidence for association of polymorphisms in the renin-angiotensin system genes with WMLs, independent of hypertension. Male-only associations with WMLs were found for the AGT rs699 and ACE rs362 polymorphisms. Moreover, for the entire sample an interaction between AGT and AGTR1 rs5182 genotypes on WMLs was observed.
白质病变（WMLs）在T2加权磁共振成像脑部扫描中表现为高信号，在健康老年人的大脑中很常见。它们被认为与脑小血管疾病有关，并且在其病因中具有遗传成分，高血压被认为是一个重要的危险因素。因此，高血压相关基因中的遗传多态性可能与WMLs的形成有关。
在本研究中，从一项更大的纵向流行病学研究“贯穿一生的人格与总体健康项目”中抽取了445名60 - 65岁的澳大利亚人作为样本。研究了编码血管紧张素原（AGT，rs699）、血管紧张素转换酶（ACE，rs4362）和1型血管紧张素II受体（AGTR1，rs5182）的基因中的单核苷酸多态性（SNP）与WMLs的关联。
对于整个样本，没有单个SNP显示出与WMLs有显著关联。当按性别对队列进行分层时，ACE rs4362和AGT rs699仅在男性中显示出与WMLs有显著关联（分别为P = 0.01和P = 0.03），并且在控制高血压后仍然显著。虽然AGTR1 SNP与WMLs没有显示出任何关联，但AGT rs699和AGTR1 rs5182 SNP与WMLs的相互作用在调整高血压之前（P = 0.03）和之后（P = 0.045）均显著。
结果为肾素 - 血管紧张素系统基因多态性与WMLs的关联提供了证据，且独立于高血压。发现AGT rs699和ACE rs362多态性仅与男性的WMLs有关联。此外，在整个样本中观察到AGT和AGTR1 rs5182基因型在WMLs上存在相互作用。
