• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Human mutation >Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans.
【24h】

Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans.

机译：WNK1基因中的新型多态AluYb8插入与欧洲人的血压变化有关。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mutations in WNK1 and WNK4 cause familial hypertension, the Gordon syndrome. WNK1 and WNK4 conserved noncoding regions were targeted to polymorphism screening using DHPLC and DGGE. The scan identified an undescribed polymorphic AluYb8 insertion in WNK1 intron 10. Screening in primates revealed that this Alu-insertion has probably occurred in human lineage. Genotyping in 18 populations from Europe, Asia, and Africa (n = 854) indicated an expansion of the WNK1 AluYb8 bearing chromosomes out of Africa. The allele frequency in Sub-Saharan Africa was ~3.3 times lower than in other populations (4.8 vs. 15.8%; P = 9.7 x 10(-9) ). Meta-analysis across three European sample sets (n = 3,494; HYPEST, Estonians; BRIGHT, the British; CADCZ, Czech) detected significant association of the WNK1 AluYb8 insertion with blood pressure (BP; systolic BP, P = 4.03 x 10(-3) , effect 1.12; diastolic BP, P = 1.21 x 10(-2) , effect 0.67). Gender-stratified analysis revealed that this effect might be female-specific (n = 2,088; SBP, P = 1.99 x 10(-3) , effect 1.59; DBP P = 3.64 x 10(-4) , effect 1.23; resistant to Bonferroni correction), whereas no statistical support was identified for the association with male BP (n = 1,406). In leucocytes, the expressional proportions of the full-length WNK1 transcript and the splice-form skipping exon 11 were significantly shifted in AluYb8 carriers compared to noncarriers. The WNK1 AluYb8 insertion might affect human BP via altering the profile of alternatively spliced transcripts.
机译：WNK1和WNK4中的突变会导致家族性高血压，即戈登综合征。使用DHPLC和DGGE将WNK1和WNK4保守的非编码区靶向多态性筛选。扫描发现在WNK1内含子10中有一个未描述的多态性AluYb8插入。灵长类动物的筛选显示，这种Alu插入可能已在人类谱系中发生。来自欧洲，亚洲和非洲（n = 854）的18个人群的基因分型表明带有WNK1 AluYb8的染色体从非洲扩展出来。撒哈拉以南非洲地区的等位基因频率比其他人群低约3.3倍（4.8比15.8％; P = 9.7 x 10（-9））。对三个欧洲样本集（n = 3,494; HYPEST，爱沙尼亚人; BRIGHT，英国; CADCZ，捷克）的荟萃分析检测到WNK1 AluYb8插入与血压（BP;收缩压，P = 4.03 x 10（- 3），效果为1.12;舒张压BP，P = 1.21 x 10（-2），效果为0.67）。性别分层分析显示，这种效应可能是女性特异性的（n = 2,088; SBP，P = 1.99 x 10（-3），效应1.59; DBP P = 3.64 x 10（-4），效应1.23;对Bonferroni有抗药性校正），而未发现与男性BP相关的统计支持（n = 1,406）。与非载体相比，在白细胞中，全长WNK1转录本和剪接形式的跳跃外显子11的表达比例在AluYb8载体中显着改变。 WNK1 AluYb8的插入可能会通过改变交替剪接的转录本的谱来影响人的BP。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号