© Springer International Publishing AG 2017 195
T. Angelone et al. (eds.), Chromogranins: from Cell Biology to Physiology
and Biomedicine, UNIPA Springer Series, DOI 10.1007/978-3-319-58338-9_12
Naturally Occurring Single Nucleotide
Polymorphisms in Human Chromogranin
A (CHGA) Gene: Association
with Hypertension and Associated Diseases
Nitish R. Mahapatra, Sajalendu Ghosh, Manjula Mahata,
Gautam K. Bandyopadhyay, and Sushil K. Mahata
Abstract Single nucleotide polymorphisms (SNPs) refer to changes of a single
DNA base, which accounts for ~90% of human sequence variations. Chromogranin
A (CgA) is a secretory protein whose plasma concentration is augmented in estab-
lished essential (hereditary) hypertension, in heart failure patients and in patients
with renal failure. Resequencing of CHGA gene in several ethnic groups across the
globe led to the discovery of both common (minor allele frequency > 5%) and rare
(minor allele frequency < 5%) SNPs in the coding and in the regulatory regions such
as the proximal promoter and 3′-UTR (untranslated region). Variants in both the
proximal promoter and the 3′-UTR showed statistical associations with hyperten-
sion. In contrast, the hypertensive renal disease was best predicted by variants at the
3 ′-UTR. Non-synonymous (change in amino acid) SNPs in the pancreastatin (PST)
and catestatin (CST) domains affected insulin-stimulated glucose uptake and nico-
tine-evoked catecholamine secretion, respectively. The heterozygote (Gly364Ser)
and minor allele homozygote (Ser364Ser) variant of CST influenced both cardio-
vascular (autonomic function and hypertension) and metabolic (plasma glucose,
We dedicate this review article to Daniel T. O’Connor who passed away on August 6, 2014. He
took the lead on the discovery and functional characterization of CHGA SNPs at UCSD.
N.R. Mahapatra
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences,
Indian Institute of Technology Madras, Chennai, India
S. Ghosh
Postgraduate Department of Zoology, Ranchi College, Ranchi, India
M. Mahata • G.K. Bandyopadhyay
Department of Medicine, University of California, San Diego, CA, USA
S.K. Mahata, Ph.D. (*)
VA San Diego Healthcare System, San Diego, CA, USA
Metabolic Physiology & Ultrastructural Biology Laboratory, Department of Medicine,
University of California, San Diego, 9500 Gilman Drive, La Jolla,
CA 92093-0732, USA
e-mail: [email protected]