209present-oriented regarding the daily management (or treatment) of hypertension as
compared to whites.
Discovery and analysis of genetic variations at the CHGA locus in geographi-
cally/ethnically-different human populations revealed the presence of functional
SNPs in the regulatory regions (viz., promoter and 3′-UTR) as well as coding
regions (viz. within PST and CST peptide domains). A significant extent of hetero-
geneity in the occurrence (presence/absence/frequency) of several of these SNPs
across different populations was observed. Nonetheless, CHGA SNPs showed
strong associations with a number of cardiovascular phenotypes (viz. blood pres-
sure, cardiac functions, plasma glucose, catecholamines and cholesterol levels).
Further studies in this area may lead to utilization of CHGA genetic variations for
clinical management of cardiovascular/metabolic disease states including hyperten-
sion and hypertensive kidney disease.
Acknowledgments Studies at UCSD were supported by grants from the National Institutes of
Health and Veterans Affairs Medical Research. Research at IIT Madras was supported by grants
from the Department of Biotechnology (BT/PR9546/MED/12/349/2007) and Science and
Engineering Research Board (SR/SO/HS-084/2013A), Govt. of India.
References
Aardal S, Helle KB, Elsayed S, Reed RK, Serck-Hanssen G (1993) Vasostatins, comprising the
N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel seg-
ments. J Neuroendocrinol 5:405–412
Allu PK, Chirasani VR, Ghosh D, Mani A, Bera AK, Maji SK, Senapati S, Mullasari AS,
Mahapatra NR (2014) Naturally occurring variants of the dysglycemic peptide pancreastatin:
differential potencies for multiple cellular functions and structure-function correlation. J Biol
Chem 289:4455–4469
Angelone T, Quintieri AM, Brar BK, Limchaiyawat PT, Tota B, Mahata SK, Cerra MC (2008) The
antihypertensive chromogranin a peptide catestatin acts as a novel endocrine/paracrine modu-
lator of cardiac inotropism and lusitropism. Endocrinology 149:4780–4793
Bandyopadhyay GK, Lu M, Avolio E, Siddiqui JA, Gayen JR, Wollam J, Vu CU, Chi NW,
O’Connor DT, Mahata SK (2015) Pancreastatin-dependent inflammatory signaling mediates
obesity-induced insulin resistance. Diabetes 64:104–116
Bandyopadhyay GK, Vu CU, Gentile S, Lee H, Biswas N, Chi NW, O’Connor DT, Mahata SK
(2012) Catestatin (chromogranin A(352-372)) and novel effects on mobilization of fat from adi-
pose tissue through regulation of adrenergic and leptin signaling. J Biol Chem 287:23141–23151
Bartolomucci A, Possenti R, Mahata SK, Fischer-Colbrie R, Loh YP, Salton SR (2011) The extended
granin family: structure, function, and biomedical implications. Endocr Rev 32:755–797
Bell DA, Taylor JA, Butler MA, Stephens EA, Wiest J, Brubaker LH, Kadlubar FF, Lucier GW (1993)
Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a
new slow-acetylator allele common in African-Americans. Carcinogenesis 14:1689–1692
Chen Y, Rao F, Rodriguez-Flores JL, Mahapatra NR, Mahata M, Wen G, Salem RM, Shih PA,
Das M, Schork NJ, Ziegler MG, Hamilton BA, Mahata SK, O’Connor DT (2008a) Common
genetic variants in the chromogranin A promoter alter autonomic activity and blood pressure.
Kidney Int 74:115–125
Chen Y, Rao F, Rodriguez-Flores JL, Mahata M, Fung MM, Stridsberg M, Vaingankar SM, Wen G,
Salem RM, Das M, Cockburn MG, Schork NJ, Ziegler MG, Hamilton BA, Mahata SK, Taupenot
Chromogranin A SNPs and Disease Association