Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men.
Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men.
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DOI：
10.1038/mp.2009.26
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发表时间：
2010-08
影响因子：
11
通讯作者：
中科院分区：
文献类型：
--
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本纵向研究检测了白色高信号病变（WML）体积的2年变化与血管紧张素II 1型和2型受体（AGTR 1 A1166 C和AGTR 2 C3123 A）基因编码多态性之间的关系。137名抑郁症患者和94名年龄在60岁或以上的非抑郁症患者入组研究。对所有受试者和获得的用于基因分型的血液样本进行标准临床评价。在基线和大约两年后获得1.5T MRI。使用半自动分割过程处理这些扫描，该过程允许计算每个时间点的WML体积。统计模型检验了WML体积变化与基因型之间的关系，同时还控制了年龄、性别、诊断分层、基线WML体积和共病脑血管危险因素。在男性中，AGTR 1 1166 A等位基因纯合子表现出WML体积的变化显着小于1166 C携带者。我们还发现，男性报告高血压与AGTR 2 3123 C等位基因表现出较小的变化，WML体积比高血压男性与3123 A等位基因，或男性没有高血压。这些多态性与女性WML体积变化之间无显著相关性。没有观察到显著的基因-基因或基因-抑郁相互作用。我们的研究结果与先前观察到的其他肾素-血管紧张素系统多态性与高血压之间关系的性别差异相平行。需要进一步的研究来确定这些观察到的关系是否继发于影响抗高血压药物反应的多态性，以及抗高血压药物是否可以减缓WML进展并降低与WML相关的发病风险。
This longitudinal study examined the relationship between 2-year change in white matter hyperintense lesion (WML) volume and polymorphisms in genes coding for the angiotensin-II type 1 and type 2 receptors, AGTR1 A1166C and AGTR2 C3123A. 137 depressed and 94 nondepressed subjects age 60 years or older were enrolled. Standard clinical evaluations were performed on all subjects and blood samples obtained for genotyping. 1.5T MRI was obtained at baseline and approximately two years later. These scans were processed using a semi-automated segmentation process which allowed for the calculation of WML volume at each time point. Statistical models tested for the relationship between change in WML volume and genotype, while also controlling for age, sex, diagnostic strata, baseline WML volume, and comorbid cerebrovascular risk factors. In men, AGTR1 1166A allele homozygotes exhibited significantly less change in WML volume than 1166C carriers. We also found that men reporting hypertension with the AGTR2 3123C allele exhibit less change in WML volume than hypertensive men with the 3123A allele, or men without hypertension. There were no significant relationships between these polymorphisms and change in WML volume in women. No significant gene-gene or gene-depression interactions were observed. Our results parallel previously observed gender differences of the relationship between other renin-angiotensin system polymorphisms and hypertension. Further work is needed to determine if these observed relationships are secondary to polymorphisms affecting response to antihypertensive medication, and if antihypertensive medications can slow WML progression and lower the risk of morbidity associated with WMLs.
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影响因子：
--
作者：
Taylor, WD;Steffens, DC;Krishnan, KRR
通讯作者：
Krishnan, KRR
影响因子：
4.9
作者：
Rubattu, S;Di Angelantonio, E;Volpe, M
通讯作者：
Volpe, M
影响因子：
1.9
作者：
Lynch, A. I.;Arnett, D. K.;Leiendecker-Foster, C.
通讯作者：
Leiendecker-Foster, C.
影响因子：
2.7
作者：
Miyaki, K.;Hara, A.;Muramatsu, M.
通讯作者：
Muramatsu, M.
影响因子：
2.3
作者：
Payne, ME;Fetzer, DL;Krishnan, KRR
通讯作者：
Krishnan, KRR