Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

J Batra; O'Mara Tracy; R Patnala; Felicity Lose; J A Clements

doi:10.1515/hsz-2012-0211

Back

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

Journal article

Open access

Peer reviewed

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

J Batra, O'Mara Tracy, R Patnala, Felicity Lose and J A Clements

Biological Chemistry, Vol.393(12), pp.1365-1390

2012

DOI: https://doi.org/10.1515/hsz-2012-0211

Files and links (2)

pdf

PDF - Published Version89.25 kBDownload View

Published VersionPDF - Published Version Open Access

url

https://doi.org/10.1515/hsz-2012-0211View

Published Version

Abstract

cancer

genome-wide association study

high-risk variants

imputation

kallikrein

single nucleotide polymorphism

tag single nucleotide polymorphism (SNP)

The Kallikrein ( KLK ) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations. © 2012 Walter de Gruyter GmbH, Berlin/Boston.

Details

Title: Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases
Authors: J Batra (Author) - Queensland University of Technology
O'Mara Tracy (Author) - Queensland University of Technology
R Patnala (Author) - Queensland University of Technology
Felicity Lose (Author) - Queensland Institute of Medical Research
J A Clements (Author) - Queensland University of Technology
Publication details: Biological Chemistry, Vol.393(12), pp.1365-1390
Publisher: Walter de Gruyter GmbH & Co. KG
Date published: 2012
DOI: 10.1515/hsz-2012-0211
ISSN: 1431-6730
Copyright note: Copyright © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. Reproduced here in accordance with the publishers copyright policy.
Organisation Unit: University of the Sunshine Coast, Queensland; Office of Research
Language: English
Record Identifier: 99450445402621
Output Type: Journal article

Metrics

9 File views/ downloads

469 Record Views

20 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Web Of Science research areas: Biochemistry & Molecular Biology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites