A major haplotype block at the rho-associated kinase 2 locus is associated with a lower risk of hypertension in a recessive manner: the HYPGENE study.
A major haplotype block at the rho-associated kinase 2 locus is associated with a lower risk of hypertension in a recessive manner: the HYPGENE study.
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DOI：
10.1291/hypres.31.1651
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发表时间：
2008-08
影响因子：
5.4
通讯作者：
Bouchard, Claude
中科院分区：
文献类型：
--
作者：
Rankinen, Tuomo;Church, Timothy;Rice, Treva;Markward, Nathan;Blair, Steven N.;Bouchard, Claude
关键词：
本研究的目的是评估Rho相关激酶2（ROCK 2）基因座的单倍型模式，并在HYPGENE研究中前瞻性地检测ROCK 2 tagSNPs与经证实的高血压患者（N=607）和健康血压正常对照者（N=586）的高血压之间的关联。Rho相关激酶（ROCK）在参与血管平滑肌收缩和内皮一氧化氮可用性的信号传导通路中发挥核心作用。使用一组严格的标准（次要等位基因频率≥ 0.05，成对r2 ≥ 0.95），我们从HapMap高加索人数据集中的109个单核苷酸多态性（tagSNPs）中鉴定出18个单倍型标记单核苷酸多态性（tagSNPs）。使用Illumina BeadStation平台对TagSNP进行基因分型。18个tagSNPs由两个连锁不平衡（LD）块组成。LD区2中由4个SNP（rs 965665、rs 10178332、rs6755196、rs 10929732）定义的单倍型与高血压风险降低相关（p=0.003）。次要等位基因的纯合子比普通等位基因携带者患高血压的风险低85%。这些关联与基线年龄、心肺功能、体重指数、性别和随访时间无关。LD块2在ROCK 2基因座的5′-末端跨越约137 kb的基因组DNA，并覆盖编码蛋白质的激酶结构域的外显子。我们的数据强烈提示ROCK 2基因座的主要单倍型阻滞与高血压的低风险相关。因此，功能突变的鉴定可以帮助开发ROCK 2特异性治疗。
The goals of our study were to evaluate the haplotype pattern at the Rho-associated kinase 2 (ROCK2) locus and prospectively test the association between the ROCK2 tagSNPs with hypertension for verified incident hypertensive patients (N=607) and healthy, normotensive controls (N=586) in a HYPGENE study. Rho-associated kinases (ROCKs) play a central role in signaling pathways that are involved in vascular smooth muscle contraction and endothelial nitric oxide availability. Using a set of stringent criteria (minor allele frequency ≥ 0.05, pairwise r2 ≥ 0.95), we identified 18 haplotype-tagging single-nucleotide polymorphisms (tagSNPs) from the 109 SNPs available in the HapMap Caucasian data set. TagSNPs were genotyped using the Illumina BeadStation platform. The 18 tagSNPs consisted of two linkage disequilibrium (LD) blocks. A haplotype defined by four SNPs (rs965665, rs10178332, rs6755196, rs10929732) in LD block 2 was recessively associated with a lower risk of hypertension (p=0.003). Homozygotes for the minor alleles had an 85% lower risk of hypertension than carriers of the common allele. The associations were independent of baseline age, cardiorespiratory fitness, body mass index, sex, and follow-up time. The LD block 2 spans about 137 kb of genomic DNA at the 5′-end of the ROCK2 locus and covers exons encoding the kinase domain of the protein. Our data strongly suggest that a major haplotype block at the ROCK2 locus is recessively associated with a lower risk of hypertension. Identification of functional mutation(s) could thus help in the development of ROCK2-specific treatments.
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影响因子：
4.8
作者：
Kureishi, Y;Kobayashi, S;Ito, M
通讯作者：
Ito, M
影响因子：
30.8
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de Bakker, PIW;Yelensky, R;Altshuler, D
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Altshuler, D
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Rankinen, Tuomo;Church, Timothy S.;Blair, Steven N.
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Blair, Steven N.
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作者：
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通讯作者：
Altshuler, D