Novel genetic variants contributing to left ventricular hypertrophy: the HyperGEN study.
Novel genetic variants contributing to left ventricular hypertrophy: the HyperGEN study.
复制标题
DOI：
10.1097/hjh.0b013e32832be612
复制
发表时间：
2009-08
影响因子：
4.9
通讯作者：
Broeckel U
中科院分区：
文献类型：
--
作者：
Arnett DK;Devereux RB;Rao DC;Li N;Tang W;Kraemer R;Claas SA;Leon JM;Broeckel U
在已确定的高血压同胞中，采用连锁和连锁不平衡分析，鉴定导致超声心动图左心室（LV）质量和相关性状变异的基因。LV肥大的HyperGEN研究通过在4个HyperGEN现场中心使用标准化方案收集的超声心动图表征了LV质量、相对壁厚（RWT）和主动脉根直径（ARD）。高通量扫描荧光检测器系统对分布在整个基因组中的387个多态性进行基因分型。连锁分析进行了基因分型结果，一旦成为885兄弟姐妹从382同胞。尽管在1、4、5、6、7、8、9、10、12、14、17和21号染色体上发现单个LOD评分峰≥ 1.2，但我们在4号染色体上的两个种族（白色和黑色）和该区域的选定候选基因（NPY 1 R、NPY 2 R、NPY 5 R、SFPR 2、CPE、IL 15、EDNRA）中观察到宽条带峰。使用LV质量指数、RWT和ARD分布极端的病例和对照，我们评估了这些表型和候选人单倍型标记单核苷酸多态性（SNP）的相关性。在黑人中，IL 15、NPY 2 R和NPY 5 R中的SNP显示出强有力的关联证据（p < 0.005）;除EDNRA外的所有候选者均显示出暗示性关联（p < 0.05）。在白人中，NPY 2 R、NPY 5 R和SFRP 2 SNP提供了与一个或多个性状相关的暗示性证据（p < 0.05）。在高血压同胞中使用连锁分析检测到的NPY 1 R、NPY 2 R、NPY 5 R、CPE、IL 15和SFRP 2的遗传变异与黑人和/或白人的LV表型相关。
To identify genes contributing to variation in echocardiographic left ventricular (LV) mass and related traits using linkage and linkage disequilibrium analysis in sibships ascertained on hypertension. The HyperGEN Study of LV hypertrophy characterized LV mass, relative wall thickness (RWT), and aortic root diameter (ARD) with echocardiograms collected using a standardized protocol at four HyperGEN field centers. A high-throughput scanning fluorescence detector system genotyped 387 polymorphisms distributed throughout the genome. Linkage analyses were conducted once genotyping results became available for 885 siblings from 382 sibships. Although single LOD score peaks ≥ 1.2 were found on chromosomes 1, 4, 5, 6, 7, 8, 9, 10, 12, 14, 17, and 21, we observed a broad band of peaks in both ethnic groups (white and black) on chromosome 4 and selected candidate genes (NPY1R, NPY2R, NPY5R, SFPR2, CPE, IL15, EDNRA) from this region. Using cases and controls from extremes of the LV mass index, RWT, and ARD distributions, we assessed associations with these phenotypes and haplotype-tagging single nucleotide polymorphisms (SNPs) in the candidates. Among blacks, SNPs in IL15, NPY2R, and NPY5R showed strong evidence for association (p < 0.005); all candidates except EDNRA showed suggestive association (p < 0.05). In whites, NPY2R, NPY5R, and SFRP2 SNPs offered suggestive evidence of association with one or more traits (p < 0.05). Genetic variation in NPY1R, NPY2R, NPY5R, CPE, IL15, and SFRP2, detected using linkage analysis in hypertensive siblings, was associated with LV phenotypes in blacks and/or whites.