Sirtuin/uncoupling protein gene variants and carotid plaque area and morphology.
Sirtuin/uncoupling protein gene variants and carotid plaque area and morphology.
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DOI：
10.1111/ijs.12623
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Rundek T
中科院分区：
文献类型：
--
作者：
Dong C;Della-Morte D;Cabral D;Wang L;Blanton SH;Seemant C;Sacco RL;Rundek T
Sirtuins和解偶联蛋白通过控制氧化应激参与心血管疾病。我们试图研究sirtuins和解偶联蛋白单核苷酸多态性与总颈动脉斑块面积和超声灰阶中位数测量的形态学之间的关系。我们分析了来自北方曼哈顿研究的1356名无卒中受试者（60%为女性，平均年龄= 68 ± 9岁）。在控制人口统计学、血管危险因素（RF）和人群分层后，采用多元线性回归模型评估11个sirtuins/解偶联蛋白基因的85个单核苷酸多态性与总斑块面积和灰度中值的相关性。我们调查了性别和RF对这些关系的影响，如果交互作用具有P <0.005，则进行分层分析。在存在斑块的个体中（55%），平均总斑块面积为20.3 ± 20.8 mm 2，灰度中值为90 ± 29。调整后，SIRT 6 rs 107251与总斑块面积显著相关（每增加一个T等位基因拷贝，β = 0.30，Bonferroni校正P = 0.005）。UCP 1中rs 1430583的T等位基因携带者在女性中显示灰度中值降低，但在男性中没有。SIRT 3中rs 4980329和rs 12363280的次要等位基因携带者在男性中具有更高的灰度中值，但在女性中没有。UCP 3基因变异与血脂异常个体的平均灰度中位数较高显著相关。我们的研究结果表明，SIRT 6/UCP 1基因多态性可能是重要的颈动脉斑块负荷和回声密度增加，但这些结果的翻译脑血管事件的个体风险需要进一步调查。女性rs 1430583、男性rs 12363280和血脂异常患者rs 1685354的显著相关性也值得进一步研究。
Sirtuins and uncoupling proteins have been implicated in cardiovascular diseases by controlling oxidative stress. We sought to investigate the association of sirtuins and uncoupling proteins single nucleotide polymorphisms with total carotid plaque area and morphology measured by ultra-sonographic gray scale median. We analyzed 1356 stroke-free subjects (60% women, mean age = 68 ± 9 years) from the Northern Manhattan Study. Multiple linear regression models were used to evaluate the association of 85 single nucleotide polymorphisms in 11 sirtuins/uncoupling protein genes with total plaque area and gray scale median after controlling for demographics, vascular risk factors (RFs), and population stratification. We investigated effect modifications of these relationship by gender and RFs and performed stratified analysis if the interaction effect had P < 0·005. Among individuals with present plaque (55%), the mean total plaque area was 20·3 ± 20·8 mm2 and gray scale median 90 ± 29. After adjustment, SIRT6 rs107251 was significantly associated with total plaque area (β = 0·30 per copy of T allele increase, Bonferroni-corrected P = 0·005). T allele carriers of rs1430583 in UCP1 showed a decreased gray scale median in women but not in men. The minor allele carriers of rs4980329 and rs12363280 in SIRT3 had higher gray scale median in men but not in women. Variants in UCP3 gene were significantly associated with higher mean gray scale median in individuals with dyslipidemia. Our findings suggest that polymorphisms in SIRT6/ UCP1 genes may be important for increased carotid plaque burden and echodensity, but translation of these findings to an individual risk of cerebrovascular events needs further investigation. Significant associations of rs1430583 in women, rs12363280 in men, and rs1685354 in those with dyslipidemia also deserve further investigations.
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