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World J Cardiol. 2014 May 26;6(5):327-37. doi: 10.4330/wjc.v6.i5.327.

Elevated blood pressure: Our family's fault? The genetics of essential hypertension.

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1
Aniket Natekar, Randi L Olds, Meghann W Lau, Kathleen Min, Karra Imoto, Thomas P Slavin, The John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, United States.

Abstract

AIM:

To provide an updated review on current genetic aspects possibly affecting essential hypertension (EH), and to further elucidate their role in EH.

METHODS:

We searched for genetic and epigenetic factors in major studies associated with EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that discussed mostly human studies, and were accessible through the university online resource. We found 11 genome wide association studies (GWAS), as well as five methylation and three miRNA studies that fit our search criteria. A distinction was not made between genes with protective effects or negative effects, as this article is only meant to be a summary of genes associated with any aspect of EH.

RESULTS:

We found 130 genes from the studies that met our inclusion/exclusion criteria. Of note, genes with multiple study references include: STK39, CYP17A1, MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the identified genes were found to have functions associated with EH. Many epigenetic factors were also correlated with EH. Of the epigenetic factors, there were no articles discussing siRNA and its effects on EH that met the search criteria, thus the topic was not included in this review. Among the miRNA targets found to be associated with EH, many of the genes involved were also identified in the GWAS studies.

CONCLUSION:

Genetic hypertension risk algorithms could be developed in the future but may be of limited benefit due to the multi-factorial nature of EH. With emerging technologies, like next-generation sequencing, more direct causal relationships between genetic and epigenetic factors affecting EH will likely be discovered creating a tremendous potential for personalized medicine using pharmacogenomics.

KEYWORDS:

Epigenomics; Essential hypertension; Genes; Genome-wide association study; MicroRNAs

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