Association between NEDD4L gene and sodium lithium countertransport.
Association between NEDD4L gene and sodium lithium countertransport.
复制标题
NEDD4L 基因与钠锂反转运之间的关联。
DOI：
10.1038/ajh.2010.222
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发表时间：
2011
影响因子：
3.2
通讯作者：
Ferrell,RobertE
中科院分区：
文献类型：
--
作者：
Zheng,Xiaojing;Morrison,AlannaC;Feingold,Eleanor;Turner,StephenT;Ferrell,RobertE
背景钠锂反向转运（SLC）是原发性高血压的一种中间表型。本研究的目的是通过基因表达谱分析和连锁分析相结合的策略来筛选SLC的候选基因，并探讨该候选基因与SLC及高血压的相关性。将基因表达微阵列中高SLC组和低SLC组之间差异表达的前1%基因与已发表的SLC/高血压基因连锁图谱，以确定重叠区域。罗切斯特家族心脏研究（RFHS）进一步评估了候选基因的遗传变异与SLC和血压表型之间的关联，该研究涉及来自252个家系的1，815名欧洲血统的个体。E3泛素蛋白连接酶NEDD 4样（NEDD 4L）被鉴定为SLC的位置和功能候选基因。逆转录-PCR（RT-PCR）分析证实了高SLC组和低SLC组之间NEDD 4L表达的差异。在调整年龄、性别和体重指数（BMI）后，发现NEDD 4L的4个单核苷酸多态性（SNP）与SLC相关（P ≤ 0.05）。此外，单倍型分析显示，经过多次测试校正，单倍型（H2）之一仍然显着（P = 0.006）与SLC.ConclusionsThe相结合的基因表达谱和连锁分析的策略成功地指导我们在确定NEDD 4L作为一个候选基因参与调节SLC活性。NEDD 4L基因的变异与SLC活性相关。美国高血压杂志，2010年11月18日提前在线出版; doi：10.1038/ajh.2010.222
BackgroundSodium lithium countertransport (SLC) is an intermediate phenotype of essential hypertension. The aim of this study was to identify candidate genes for SLC by a strategy of combining gene expression profiling and linkage analysis, and to examine the association between the candidate gene and SLC as well as hypertension.MethodsIn order to identify SLC-related genes, the top 1% of the genes that were differentially expressed between high- and low-SLC groups in a gene expression microarray were compared with published SLC/ hypertension gene linkage maps so as to identify regions of overlap. The association between the genetic variation in the candidate gene and the SLC and blood pressure phenotypes were further assessed in the Rochester Family Heart Study (RFHS) involving 1,815 individualsof European ancestry, belonging to 252 pedigrees.ResultsBased on gene expression profiling and evidence from genome-wide linkage analysis, and in the light of its potential biochemical function, E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as being both a positional and a functional candidate gene for SLC. The difference in expressions of NEDD4L between the high- and low-SLC groups was confirmed by reverse transcription-PCR (RT-PCR) analysis. After adjusting for age, sex, and body mass index (BMI), four single-nucleotide polymorphisms (SNPs) in NEDD4L were found to be associated with SLC (P ≤ 0.05). Further, haplotype analysis revealed that, after correction for multiple testing, one of the haplotypes (H2) was still significantly (P = 0.006) associated with SLC.ConclusionsThe strategy of combining gene expression profiling and linkage analysis successfully guided us in identifying NEDD4L as a candidate gene involved in regulating SLC activity. Variations in the NEDD4L gene are associated with SLC activity.American Journal of Hypertension, advance online publication 18 November 2010; doi:10.1038/ajh.2010.222