Gender-specific influence of NO synthase gene on blood pressure since childhood - The Bogalusa Heart Study
Gender-specific influence of NO synthase gene on blood pressure since childhood - The Bogalusa Heart Study
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DOI：
10.1161/01.hyp.0000145474.23750.2b
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发表时间：
2004-11-01
期刊：
影响因子：
8.3
通讯作者：
Berenson, GS
中科院分区：
文献类型：
--
作者：
Chen, W;Srinivasan, SR;Berenson, GS
NO生成减少引起的内皮功能受损在原发性高血压中起着病理生理作用。虽然关于内皮型NO合酶基因多态性与高血压之间的关联的横断面数据是可用的，但基因变异及其单倍型是否会影响儿童期以来血压的长期累积负担和趋势尚不清楚。这方面进行了检查，使用4个多态性和一个基于社区的纵向队列的347名黑人和801名白人，年龄在18至45岁，已连续检查4至13次（7705观察），平均23.4年。使用平均动脉压连续测量的生长曲线计算的曲线下面积用作长期累积负荷。与白人相比，黑人显示G894 T（0.112对0.325），G10 T（0.209对0.323），T-786 C（0.147对0.372）和A-922 G（0.131对0.355）的罕见等位基因频率显著较低。此外，T-786 C和A-922 G多态性在两个种族中处于完全连锁不平衡。校正年龄和体重指数后，894 T和10 T等位基因分别与黑人女性和白色女性自童年以来较低的长期血压负担显著相关。在单倍型方面，与（G894-G10）/（G894-G10）相比，G894- 10 T携带者在白色女性中显示出显著较低的长期血压负担和趋势。总之，内皮型一氧化氮合酶基因影响了女性自童年以来血压的长期负担和趋势，并可能导致其易患高血压。
Impaired endothelial function caused by decreased NO production plays a pathophysiologic role in essential hypertension. Although cross-sectional data are available on the association between endothelial NO synthase gene polymorphisms and hypertension, whether the gene variants and their haplotypes affect the long-term cumulative burden and trend of blood pressure since childhood is not known. This aspect was examined using 4 polymorphisms and a community-based longitudinal cohort of 347 blacks and 801 whites aged 18 to 45 years who have been examined serially 4 to 13 times (7705 observations) over an on average of 23.4 years. The area under the curve calculated using a growth curve of serial measurements of mean arterial pressure was used as a long-term cumulative burden. Blacks compared with whites displayed significantly lower frequencies of the rare alleles for G894T (0.112 versus 0.325), G10T (0.209 versus 0.323), T-786C (0.147 versus 0.372), and A-922G (0.131 versus 0.355). In addition, T-786C and A-922G polymorphisms were in complete linkage disequilibrium in both races. After adjusting for age and body mass index, the 894T and 10T alleles were significantly associated with lower long-term burden of blood pressure since childhood in black females and white females, respectively. With respect to haplotypes, the G894-10T carriers compared with (G894-G10)/(G894-G10) showed significantly lower long-term burden and trend of blood pressure in white females. In conclusion, the endothelial NO synthase gene influences the long-term burden and trend of blood pressure since childhood in females and may contribute to their predisposition to hypertension.